Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine

• Sponsor: PATH (Other)
• Overall Status: Completed
• CT.gov ID: NCT03300050
• Collaborator: Icahn School of Medicine at Mount Sinai (Other), Children's Hospital Medical Center, Cincinnati (Other), Duke University (Other), The Emmes Company, LLC (Industry), GlaxoSmithKline (Industry)
• Enrollment: 65
• Locations: 2
• Arms: 5
• Actual Duration (Months): 21.9
• Patients Per Site: 32.5
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The clinical study will evaluate safety and the immune response of a prime- boost regimen with a live attenuated influenza vaccine (LAIV) prime and an inactivated split influenza vaccine (IIV) boost with or without adjuvant.

Condition or Disease	Intervention/Treatment	Phase
Influenza; Vaccine	Biological: cH8/1N1 LAIV; Biological: AS03-adjuvanted cH5/1N1 IIV; Biological: cH5/1N1 IIV; Biological: AS03-adjuvanted cH8/1N1 IIV; Biological: Normal saline; Biological: Phosphate buffered saline (PBS)	Phase 1

Detailed Description

This is a prospective, multi-center, randomized, controlled, observer-blind, Phase 1 trial in healthy male and female adults 18 through 39 years of age to evaluate safety and the immune response of a prime boost regimen with LAIV prime and IIV boost with or without adjuvant. Participants will be randomized 4:3:1:3:2 to one of five groups to receive a first dose of study cH8/1N1 LAIV (or placebo) or study cH8/1N1 IIV + AS03A adjuvant (or placebo) followed three months later by study cH5/1N1 IIV +/- AS03A adjuvant (or placebo).

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Eligible enrolled subjects will be randomized to any of the treatment arms (LAIV-IIV, Groups 1, 2, and 3; or IIV-IIV, Groups 4 and 5) under one allocation sequence, stratified by site, to allow comparability between study groups, such as LAIV-IIV vs IIV-IIV regimens (Groups 1 vs 4). Groups 1-3 will be inpatient and receive either LAIV or placebo as nasal drops at Dose 1. Groups 4-5 ill be outpatient and receive either IIV or placebo as an injection at Dose 1.Eligible enrolled subjects will be randomized to any of the treatment arms (LAIV-IIV, Groups 1, 2, and 3; or IIV-IIV, Groups 4 and 5) under one allocation sequence, stratified by site, to allow comparability between study groups, such as LAIV-IIV vs IIV-IIV regimens (Groups 1 vs 4). Groups 1-3 will be inpatient and receive either LAIV or placebo as nasal drops at Dose 1. Groups 4-5 ill be outpatient and receive either IIV or placebo as an injection at Dose 1.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: An unblinded pharmacist will prepare Dose 1 and Dose 2. Participants and study staff will remain blinded to their exact treatment group but will be unblinded to their overall group allocation (inpatient or outpatient).
• Primary Purpose: Prevention
• Official Title: A Phase 1, Randomized, Controlled, Observer-blind Study to Assess the Reactogenicity, Safety, and Immunogenicity of a Live Attenuated Universal Influenza Vaccine (cH8/1N1 LAIV) Administered as a Single Priming Dose Followed Three Months Later by a Single Booster Dose of an Inactivated Universal Influenza Vaccine (cH5/1N1 IIV) (Adjuvanted With AS03A or Unadjuvanted) in 18 Through 39 Year-old Healthy Subjects, Contrasted With a Two Dose Schedule of an Inactivated Universal Influenza Vaccine (cH8/1N1 IIV + AS03A Followed Three Months Later by cH5/1N1 IIV + AS03A)
• Actual Study Start Date: Oct 10, 2017
• Actual Primary Completion Date: Apr 24, 2018
• Actual Study Completion Date: Aug 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + adjuvant Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Biological: cH8/1N1 LAIV; Live-attenuated influenza virus vaccine (LAIV) expressing chimeric hemagglutinin (HA) with the H8 head and H1 stalk and neuraminidase (NA) subtype 1 (N1) (cH8/1N1): HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1) containing the backbone of the cold-adapted/temperature sensitive of the Russian LAIV A/Leningrad/134/17/1957 (Len17 IDCDCRG46D). Administered intranasally as drops at a dose of 10⁷·⁵ (plus or minus ⁰·⁵) 50% egg infectious dose (EID50), formulated in a total volume of 0.5 mL sterile saline (0.25 mL per nostril).; Biological: AS03-adjuvanted cH5/1N1 IIV; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV) plus AS03 adjuvant: HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1). Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Other Names: cH5/1N1 IIV + AS03 adjuvant
Experimental: Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Biological: cH8/1N1 LAIV; Live-attenuated influenza virus vaccine (LAIV) expressing chimeric hemagglutinin (HA) with the H8 head and H1 stalk and neuraminidase (NA) subtype 1 (N1) (cH8/1N1): HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1) containing the backbone of the cold-adapted/temperature sensitive of the Russian LAIV A/Leningrad/134/17/1957 (Len17 IDCDCRG46D). Administered intranasally as drops at a dose of 10⁷·⁵ (plus or minus ⁰·⁵) 50% egg infectious dose (EID50), formulated in a total volume of 0.5 mL sterile saline (0.25 mL per nostril).; Biological: cH5/1N1 IIV; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV): HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1). Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).
Placebo Comparator: Group 3: Placebo Participants received 0.5 mL of normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Biological: Normal saline; Administered intranasally as 0.25 mL nasal drops per nostril; Biological: Phosphate buffered saline (PBS); Administered intramuscularly as 0.5 mL injection
Experimental: Group 4: cH8/1N1 IIV + adjuvant and cH5/1N1 IIV + adjuvant Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Biological: AS03-adjuvanted cH5/1N1 IIV; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV) plus AS03 adjuvant: HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1). Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Other Names: cH5/1N1 IIV + AS03 adjuvant ; Biological: AS03-adjuvanted cH8/1N1 IIV; Chimeric H8 head with H1 stalk plus N1 (cH8/1N1) inactivated influenza vaccine plus AS03 adjuvant: HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1). Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Other Names: cH8/1N1 IIV + AS03 adjuvant
Placebo Comparator: Group 5: Placebo Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.	Biological: Phosphate buffered saline (PBS); Administered intramuscularly as 0.5 mL injection

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination [7 days after each vaccination (Days 1-8 and Days 85-92)]

   Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited local reactions included: Post LAIV dose: nasal congestion, rhinorrhea; Post IIV dose: pain, redness, swelling.

2. Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination [7 days after each vaccination (Days 1-8 and Days 85-92)]

   Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited general reactions included: abdominal pain arthralgia cough diarrhea fatigue fever headache myalgia nausea shivering sore throat vomiting wheezing

3. Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination [28 days after each vaccination (Days 1 to 28 and Days 85 to 113)]

   Unsolicited adverse events (AEs) are any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents, such as diary cards. Participants were asked to record any unsolicited symptoms or other illness description in their diary card during the 28 days after each vaccination. All AEs, including clinical laboratory test results, were assessed by a study clinician and the study subject (as applicable) to quantify severity using a protocol-defined grading system as mild (mild symptoms, easily tolerated, not interfering with daily activities), moderate (causing some interference with daily activity), or severe (severe symptoms that prevent normal every day activities). The investigator assessed the relationship between study vaccines and the occurrence of each AE using clinical judgment.

4. Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 [Days 8, 29, 85, 92, and 113]

   Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio. Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening). Grade 2 or higher: BUN: > 26 mg/dL Creatinine: > 1.7 mg/dL ALT, AST: > 2.5 × upper limit of normal (ULN) Hemoglobin: < 11.0 g/dL (females) or < 12.5 g/dL (males) or change from baseline > 1.5 g/dL WBC: > 15,000 cell/mm³ or < 2,500 cell/mm³ Lymphocytes: < 750 cell/mm³ ANC: < 1,500 cell/mm³ Eosinophils: > 1,500 cell/mm³ Platelets: < 125,000 cell/mm³

5. Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113 [Through Day 113 (28 days post-dose 2)]

   An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by polymerase chain reaction (PCR) assay. An SAE is an AE that met any of the following: Death Life threatening Required inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Results in congenital anomaly/birth defect An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.

Secondary Outcome Measures

1. Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 [Month 9 (6 months post-dose 2) and Month 15 (12 months post-dose 2)]

   Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio. Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening). Grade 2 or higher: BUN: > 26 mg/dL Creatinine: > 1.7 mg/dL ALT, AST: > 2.5 × upper limit of normal (ULN) Hemoglobin: < 11.0 g/dL (females) or < 12.5 g/dL (males) or change from baseline > 1.5 g/dL WBC: > 15,000 cell/mm³ or < 2,500 cell/mm³ Lymphocytes: < 750 cell/mm³ ANC: < 1,500 cell/mm³ Eosinophils: > 1,500 cell/mm³ Platelets: < 125,000 cell/mm³

2. Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study [From first dose to end of study, 588 days (21 months; 18 months post-dose 2)]

   An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by PCR assay. An SAE is an AE that met any of the following: Death Life threatening Required inpatient hospitalization or prolongation of existing hospitalization Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Resulted in congenital anomaly/birth defect An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.

3. Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5 [Days 1 to 5]

   To detect viral shedding participants who received LAIV vaccine or intranasal sterile saline as the prime dose had nasal and oropharyngeal swabs collected on Days 1 to 5. Influenza type A virus ribonucleic acid (RNA) was detected using reverse transcription polymerase chain reaction (RT-PCR).

4. Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination [Days 1 to 5]

   To study virus infectivity, nasal and oropharyngeal swab specimens that tested influenza A positive by RT-PCR were further tested for viability of virus in Madin Darby canine kidney (MDCK) cell culture and stained with monoclonal antibody specific to the cH8/1N1 LAIV virus to confirm detected virus is of vaccine origin.

5. Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)]

   Anti-H1 hemagglutinin (HA) stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 65.3 EU/mL.

6. Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)]

   Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The lower limit of quantitation (LLOQ) for the assay was 65.3 EU/mL.

7. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)]

   Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

8. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)]

   Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

9. Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)]

   Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

10. Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin A Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:100.

11. Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

12. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

13. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .

14. Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

15. Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 [H6N1]) and the H1 stalk domain (strain A/California/04/2009 [H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.

16. Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). The LLOQ for the assay was 1:10.

17. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).

18. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).

19. Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 [H6N1]) and the H1 stalk domain (strain A/California/04/2009 [H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

20. Serum Antibody-dependent Cell-mediated Cytotoxicity (ADCC) to the H1 Hemagglutinin Stalk [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured in relative luciferase units (RLU) for serial dilutions of serum samples using a plate reader. ADCC activity was expressed by the area under the curve (AUC) of luminescence (RLU) per serial dilution (X-fold serial dilutions).

21. Fold-Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.

22. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.

23. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.

24. Percentage of Participants With Anti-H1 Hemagglutinin Stalk Salivary IgG Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:10.

25. Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:10.

26. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

27. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

28. Mean Geometric Increase of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

29. Percentage of Participants With Anti-H1 Hemagglutinin Stalk Secretory IgA Antibody Seropositivity in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:4.

30. Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:4.

31. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

32. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

33. Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

34. Percentage of Participants With Anti-H1 Hemagglutinin Stalk Total IgA Antibody Seropositivity in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:10.

35. Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:10.

36. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

37. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).

38. Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

39. Percentage of Participants With Serum Anti-H2 Full-length Hemagglutinin IgG Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 22.

40. Geometric Mean Titer of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.

41. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.

42. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.

43. Mean Geometric Increase of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

44. Percentage of Participants With Serum Anti-H9 Full-length Hemagglutinin IgG Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 31.

45. Geometric Mean Titer of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The LLOQ for the assay was 31 EU/mL.

46. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.

47. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length(ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.

48. Mean Geometric Increase of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

49. Percentage of Participants With Serum Anti-H18 Full-length Hemagglutinin IgG Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 42.3.

50. Geometric Mean Titer of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.

51. Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.

52. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.

53. Mean Geometric Increase of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

54. Percentage of Participants With Serum Anti-Human H1N1 Virus Neutralizing Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.

55. Geometric Mean Titer of Serum Anti-Human H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). The LLOQ for the assay was 1:10.

56. Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Human H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).

57. Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-Human H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).

58. Mean Geometric Increase of Serum Anti-Human H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

59. Percentage of Participants With Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.

60. Geometric Mean Titer of Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). The LLOQ for the assay was 1:10.

61. Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).

62. Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).

63. Mean Geometric Increase From Baseline in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

64. Percentage of Participants With Serum Anti-H5N8 Virus Neutralizing Antibody Seropositivity [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on Puerto Rico (PR)/8 for 6 genes with 2 surface proteins: HA and neuraminidase (NA) from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.

65. Geometric Mean Titer of Serum Anti-H5N8 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). The LLOQ for the assay was 1:10.

66. Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).

67. Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).

68. Mean Geometric Increase From Baseline in Serum Anti-H5N8 Virus Neutralizing Antibodies [Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)]

    This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination prior to vaccination.

• In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).

• Written informed consent obtained from the subject prior to performance of any study specific procedure.

• Male or non-pregnant female between, and including, 18 and 39 years of age at the time of the first vaccination.

• Healthy subjects without acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality*.

• Female subjects of non-childbearing potential may be enrolled in the study.

• Female subjects of childbearing potential must have a negative pregnancy test within 24 hours of vaccination.

• Female subjects of childbearing potential must have practiced adequate contraception for 30 days prior to first vaccination and agree to continue adequate contraception until 2 months after completion of the vaccination series (Month 5).

• Male subjects must be surgically sterile (e.g., vasectomy) or agree to practice adequate contraception from the first vaccination until 2 months after completion of the vaccination series (Month 5). Please refer to the glossary of terms for the definition of adequate contraception.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines.

• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.

• Medically diagnosed deviated nasal septum or nasal obstruction.

• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months before the first dose.

• Administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab) within 6 months before the first dose (Visit 03), or planned administration any time during the study period.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose (Visit 03) up to Month 15 (Visit

• Persons who should be annually vaccinated against influenza who live with or care for persons at high risk for influenza-related complications.

• History of influenza vaccination within 6 months prior to study enrollment or unwillingness to forego seasonal influenza vaccination during the entire study period.

• History of vaccination with an investigational pandemic influenza vaccine other than an 2009 H1N1 Pandemic (H1N1pdm09) vaccine.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• Infection with human immunodeficiency virus regardless of clinical stage of immunodeficiency.

• History of current infection with hepatitis B virus or hepatitis C virus regardless of clinical presentation.

• History of or current autoimmune disease.

• Subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of narcolepsy in a subject's parent or sibling.

• History of Guillain-Barré syndrome.

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.

• Hypersensitivity to latex.

• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period.

• Pregnant or lactating female.

• Female planning to become pregnant or male planning to father a child or either planning to discontinue contraceptive precautions.

• Current smoker.

• During screening, have a positive test for opiates without a prescription.

• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.

• Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.

• Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.

• Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.

• Blood donation or planned blood donation within 30 days prior to the study vaccination through 30 days after the last blood drawn for this study.

• Have signs or symptoms that could confound or confuse assessment of study vaccine reactogenicity.

• Any hematological or biochemical parameter that is out of range of normal, and is considered clinically significant by the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University	Durham	North Carolina	United States	27710
2	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• PATH
• Icahn School of Medicine at Mount Sinai
• Children's Hospital Medical Center, Cincinnati
• Duke University
• The Emmes Company, LLC
• GlaxoSmithKline

Investigators

• Principal Investigator: David Bernstein, MD, Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Jeffrey Guptill, MD, Duke University

Study Documents (Full-Text)

• Study Protocol - Dec 9, 2018
• Statistical Analysis Plan - Oct 18, 2019

More Information

Publications

None provided.

• Responsible Party: PATH
• ClinicalTrials.gov Identifier: NCT03300050
• Other Study ID Numbers: CVIA 057 (1082166-1)
• First Posted: Oct 3, 2017
• Last Update Posted: Feb 21, 2021
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by PATH: live attenuated influenza vaccine; inactivated influenza vaccine
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the community and enrolled at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA) and the Duke Early Phase Clinical Research Unit (Durham, NC, USA) between October 10, 2017, and November 27, 2017.
Pre-assignment Detail	Participants were randomly assigned in a 4:3:1:3:2 ratio to one of five treatment groups. Randomization was blocked (block size 13) and stratified by site. Participants received two sequential study vaccinations, an initial priming dose on Day 1 followed by a booster dose on Day 85.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL chimeric H8/1N1 live-attenuated influenza virus vaccine (cH8/1N1 LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03 (Adjuvant System 03)-adjuvanted chimeric H5/1N1 inactivated influenza virus vaccine (cH5/1N1 IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted chimeric H8/1N1 inactivated influenza vaccine (cH8/1N1 IIV) administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Period Title: Overall Study
STARTED	20	15	5	16	10
Received Treatment	19	14	3	15	10
Received All Scheduled Treatments	16	13	2	15	10
COMPLETED	17	13	2	15	9
NOT COMPLETED	3	2	3	1	1

Baseline Characteristics

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo	Total
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.	Total of all reporting groups
Overall Participants	20	15	5	16	10	66
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.9 (5.3)	27.5 (5.9)	25.0 (3.7)	30.3 (5.5)	29.3 (4.6)	28.9 (5.3)
Sex: Female, Male (Count of Participants)
Female	14 70%	10 66.7%	2 40%	10 62.5%	5 50%	41 62.1%
Male	6 30%	5 33.3%	3 60%	6 37.5%	5 50%	25 37.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 13.3%	1 20%	0 0%	0 0%	3 4.5%
Not Hispanic or Latino	20 100%	13 86.7%	4 80%	16 100%	10 100%	63 95.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 20%	0 0%	0 0%	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	15 75%	10 66.7%	4 80%	14 87.5%	7 70%	50 75.8%
White	5 25%	3 20%	0 0%	2 12.5%	3 30%	13 19.7%
More than one race	0 0%	1 6.7%	0 0%	0 0%	0 0%	1 1.5%
Unknown or Not Reported	0 0%	1 6.7%	0 0%	0 0%	0 0%	1 1.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination
Description	Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited local reactions included: Post LAIV dose: nasal congestion, rhinorrhea; Post IIV dose: pain, redness, swelling.
Time Frame	7 days after each vaccination (Days 1-8 and Days 85-92)

Outcome Measure Data

Analysis Population Description

Participants who received the priming dose and booster dose

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Any Local Reacton	10 50%	2 13.3%	0 0%	11 68.8%	1 10%
Nasal Congestion	4 20%	1 6.7%	0 0%	NA NaN	NA NaN
Rhinorrhea	8 40%	2 13.3%	0 0%	NA NaN	NA NaN
Pain	NA NaN	NA NaN	NA NaN	11 68.8%	1 10%
Redness	NA NaN	NA NaN	NA NaN	1 6.3%	0 0%
Swelling	NA NaN	NA NaN	NA NaN	1 6.3%	0 0%
Any Local Reacton	10 50%	1 6.7%	0 0%	8 50%	0 0%
Nasal Congestion	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN
Rhinorrhea	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN
Pain	10 50%	1 6.7%	0 0%	8 50%	0 0%
Redness	0 0%	0 0%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination
Description	Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited general reactions included: abdominal pain arthralgia cough diarrhea fatigue fever headache myalgia nausea shivering sore throat vomiting wheezing
Time Frame	7 days after each vaccination (Days 1-8 and Days 85-92)

Outcome Measure Data

Analysis Population Description

Participants who received the priming dose and booster dose

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Post Prime Dose: Any General Reaction	13 65%	8 53.3%	1 20%	10 62.5%	4 40%
Post Prime Dose: Fever	0 0%	0 0%	0 0%	0 0%	0 0%
Post Prime Dose: Shivering	3 15%	0 0%	0 0%	1 6.3%	0 0%
Post Prime Dose: Fatigue	3 15%	4 26.7%	0 0%	6 37.5%	3 30%
Post Prime Dose: Headache	7 35%	4 26.7%	1 20%	6 37.5%	2 20%
Post Prime Dose: Myalgia	4 20%	2 13.3%	0 0%	6 37.5%	0 0%
Post Prime Dose: Arthralgia	0 0%	3 20%	0 0%	2 12.5%	0 0%
Post Prime Dose: Nausea	3 15%	3 20%	0 0%	0 0%	1 10%
Post Prime Dose: Vomiting	1 5%	0 0%	0 0%	0 0%	0 0%
Post Prime Dose: Abdominal Pain	2 10%	2 13.3%	0 0%	2 12.5%	2 20%
Post Prime Dose: Diarrhea	0 0%	0 0%	0 0%	2 12.5%	1 10%
Post Prime Dose: Sore Throat	2 10%	1 6.7%	0 0%	0 0%	0 0%
Post Prime Dose: Cough	4 20%	0 0%	0 0%	1 6.3%	0 0%
Post Prime Dose: Wheezing	0 0%	0 0%	0 0%	0 0%	0 0%
Post Booster Dose: Any General Reaction	10 50%	5 33.3%	0 0%	5 31.3%	1 10%
Post Booster Dose : Fever	0 0%	0 0%	0 0%	0 0%	0 0%
Post Booster Dose: Shivering	2 10%	2 13.3%	0 0%	1 6.3%	0 0%
Post Booster Dose: Fatigue	8 40%	3 20%	0 0%	2 12.5%	1 10%
Post Booster Dose : Headache	4 20%	4 26.7%	0 0%	0 0%	1 10%
Post Booster Dose: Myalgia	5 25%	1 6.7%	0 0%	1 6.3%	0 0%
Post Booster Dose: Arthralgia	4 20%	2 13.3%	0 0%	0 0%	0 0%
Post Booster Dose: Nausea	3 15%	2 13.3%	0 0%	0 0%	0 0%
Post Booster Dose: Vomiting	0 0%	0 0%	0 0%	0 0%	0 0%
Post Booster Dose: Abdominal Pain	2 10%	1 6.7%	0 0%	1 6.3%	0 0%
Post Booster Dose: Diarrhea	0 0%	1 6.7%	0 0%	0 0%	0 0%
Post Booster Dose: Sore Throat	3 15%	2 13.3%	0 0%	0 0%	0 0%
Post Booster Dose: Cough	1 5%	1 6.7%	0 0%	1 6.3%	0 0%
Post Booster Dose: Wheezing	0 0%	1 6.7%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination
Description	Unsolicited adverse events (AEs) are any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents, such as diary cards. Participants were asked to record any unsolicited symptoms or other illness description in their diary card during the 28 days after each vaccination. All AEs, including clinical laboratory test results, were assessed by a study clinician and the study subject (as applicable) to quantify severity using a protocol-defined grading system as mild (mild symptoms, easily tolerated, not interfering with daily activities), moderate (causing some interference with daily activity), or severe (severe symptoms that prevent normal every day activities). The investigator assessed the relationship between study vaccines and the occurrence of each AE using clinical judgment.
Time Frame	28 days after each vaccination (Days 1 to 28 and Days 85 to 113)

Outcome Measure Data

Analysis Population Description

Participants who received at least one study vaccination

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Any adverse events	10 50%	8 53.3%	1 20%	6 37.5%	5 50%
AEs related to study vaccine	5 25%	2 13.3%	0 0%	1 6.3%	0 0%
Mild adverse events	6 30%	3 20%	0 0%	3 18.8%	3 30%
Mild AEs related to study vaccine	5 25%	0 0%	0 0%	0 0%	0 0%
Moderate adverse events	3 15%	4 26.7%	1 20%	3 18.8%	2 20%
Moderate AEs related to study vaccine	0 0%	2 13.3%	0 0%	1 6.3%	0 0%
Severe adverse events	1 5%	1 6.7%	0 0%	0 0%	0 0%
Severe AEs related to study vaccine	0 0%	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113
Description	Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio. Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening). Grade 2 or higher: BUN: > 26 mg/dL Creatinine: > 1.7 mg/dL ALT, AST: > 2.5 × upper limit of normal (ULN) Hemoglobin: < 11.0 g/dL (females) or < 12.5 g/dL (males) or change from baseline > 1.5 g/dL WBC: > 15,000 cell/mm³ or < 2,500 cell/mm³ Lymphocytes: < 750 cell/mm³ ANC: < 1,500 cell/mm³ Eosinophils: > 1,500 cell/mm³ Platelets: < 125,000 cell/mm³
Time Frame	Days 8, 29, 85, 92, and 113

Outcome Measure Data

Analysis Population Description

Participants who received at least one study vaccination

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Hemoglobin	0 0%	2 13.3%	0 0%	3 18.8%	1 10%
Hemoglobin change from baseline	3 15%	1 6.7%	2 40%	3 18.8%	0 0%
Platelets	0 0%	0 0%	0 0%	0 0%	0 0%
White blood cell count	0 0%	0 0%	0 0%	0 0%	0 0%
Absolute neutrophil count	5 25%	1 6.7%	0 0%	3 18.8%	0 0%
Lymphocytes	0 0%	0 0%	0 0%	0 0%	0 0%
Basophils	0 0%	0 0%	0 0%	0 0%	0 0%
Monocytes	0 0%	0 0%	0 0%	0 0%	0 0%
Eosinophils	1 5%	0 0%	0 0%	0 0%	0 0%
Red blood cells	0 0%	0 0%	0 0%	0 0%	0 0%
Creatinine	0 0%	0 0%	0 0%	0 0%	0 0%
Blood urea nitrogen	0 0%	0 0%	0 0%	0 0%	0 0%
BUN to creatinine ratio	0 0%	0 0%	0 0%	0 0%	0 0%
Alanine aminotransferase	0 0%	0 0%	0 0%	0 0%	0 0%
Asparate aminotransferase	0 0%	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113
Description	An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by polymerase chain reaction (PCR) assay. An SAE is an AE that met any of the following: Death Life threatening Required inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Results in congenital anomaly/birth defect An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.
Time Frame	Through Day 113 (28 days post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants who received at least one study vaccination

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
SAEs	0 0%	0 0%	1 20%	0 0%	0 0%
MAEs	6 30%	2 13.3%	0 0%	3 18.8%	1 10%
LC-ILIs	0 0%	0 0%	1 20%	0 0%	0 0%
pIMDs	0 0%	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15
Description	Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio. Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening). Grade 2 or higher: BUN: > 26 mg/dL Creatinine: > 1.7 mg/dL ALT, AST: > 2.5 × upper limit of normal (ULN) Hemoglobin: < 11.0 g/dL (females) or < 12.5 g/dL (males) or change from baseline > 1.5 g/dL WBC: > 15,000 cell/mm³ or < 2,500 cell/mm³ Lymphocytes: < 750 cell/mm³ ANC: < 1,500 cell/mm³ Eosinophils: > 1,500 cell/mm³ Platelets: < 125,000 cell/mm³
Time Frame	Month 9 (6 months post-dose 2) and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants who received at least one study vaccination

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Hemoglobin	0 0%	1 6.7%	0 0%	2 12.5%	0 0%
Hemoglobin change from baseline	0 0%	1 6.7%	1 20%	2 12.5%	0 0%
Platelets	0 0%	0 0%	0 0%	0 0%	0 0%
White blood cell count	1 5%	0 0%	0 0%	0 0%	0 0%
Absolute neutrophil count	0 0%	0 0%	0 0%	0 0%	0 0%
Lymphocytes	0 0%	0 0%	0 0%	0 0%	0 0%
Basophils	0 0%	0 0%	0 0%	0 0%	0 0%
Monocytes	0 0%	0 0%	0 0%	0 0%	0 0%
Eosinophils	1 5%	0 0%	0 0%	0 0%	0 0%
Red blood cells	0 0%	0 0%	0 0%	0 0%	0 0%
Creatinine	0 0%	0 0%	0 0%	0 0%	0 0%
Blood urea nitrogen	0 0%	0 0%	0 0%	0 0%	0 0%
BUN to creatinine ratio	0 0%	0 0%	0 0%	0 0%	0 0%
Alanine aminotransferase	0 0%	0 0%	0 0%	0 0%	0 0%
Asparate aminotransferase	0 0%	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study
Description	An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by PCR assay. An SAE is an AE that met any of the following: Death Life threatening Required inpatient hospitalization or prolongation of existing hospitalization Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Resulted in congenital anomaly/birth defect An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.
Time Frame	From first dose to end of study, 588 days (21 months; 18 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants who received at least one study vaccination

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
SAEs	0 0%	0 0%	1 20%	0 0%	2 20%
MAEs	7 35%	4 26.7%	0 0%	4 25%	4 40%
LC-ILIs	1 5%	1 6.7%	1 20%	0 0%	0 0%
pIMDs	0 0%	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5
Description	To detect viral shedding participants who received LAIV vaccine or intranasal sterile saline as the prime dose had nasal and oropharyngeal swabs collected on Days 1 to 5. Influenza type A virus ribonucleic acid (RNA) was detected using reverse transcription polymerase chain reaction (RT-PCR).
Time Frame	Days 1 to 5

Outcome Measure Data

Analysis Population Description

Participants who received LAIV (Groups 1, 2, and 3) with evaluable samples

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3
Overall	7 35%	8 53.3%	0 0%
Day 2	7 35%	4 26.7%	0 0%
Day 3	1 5%	1 6.7%	0 0%
Day 4	0 0%	0 0%	0 0%
Day 5	0 0%	3 20%	0 0%

9. Secondary Outcome

Title	Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination
Description	To study virus infectivity, nasal and oropharyngeal swab specimens that tested influenza A positive by RT-PCR were further tested for viability of virus in Madin Darby canine kidney (MDCK) cell culture and stained with monoclonal antibody specific to the cH8/1N1 LAIV virus to confirm detected virus is of vaccine origin.
Time Frame	Days 1 to 5

Outcome Measure Data

Analysis Population Description

Participants who received LAIV (Groups 1, 2, and 3) and tested positive for influenza A virus by RT-PCR at any time during the 5 days post LAIV dose and with evaluable samples

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.
Measure Participants	7	7	0
Overall	0 0%	0 0%
Day 2	0 0%	0 0%
Day 3	0 0%	0 0%
Day 5	0 0%

10. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity
Description	Anti-H1 hemagglutinin (HA) stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 65.3 EU/mL.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 9 (6 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

11. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The lower limit of quantitation (LLOQ) for the assay was 65.3 EU/mL.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	11503	10213	12966	12028	8615
Month 1 (28 days post-dose 1)	11337	10347	11832	84207	7975
Month 4 (28 days post-dose 2)	62238	22073	10628	62992	9226
Month 9 (6 months post-dose 2)	19955	10846	8364	31228	7043
Month 15 (12 months post-dose 2)	16046	13470	16195	27323	6825

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted Geometric Mean Titer (GMT) Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	2.73
	Confidence Interval	(2-Sided) 95%; 1.73 to 4.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9411
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.68 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

12. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	80.0 500%	0.0 0%
Month 4 (28 days post-dose 2)	75.0 375%	15.4 102.7%	0.0 0%	57.1 356.9%	0.0 0%
Month 9 (6 months post-dose 2)	6.7 33.5%	0.0 0%	0.0 0%	21.4 133.8%	0.0 0%
Month 15 (12 months post-dose 2)	7.1 35.5%	15.4 102.7%	0.0 0%	23.1 144.4%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	59.6
	Confidence Interval	(2-Sided) 95%; 23.59 to 81.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4421
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	17.9
	Confidence Interval	(2-Sided) 95%; -16.24 to 49.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0461
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-41.8
	Confidence Interval	(2-Sided) 95%; -68.75 to -4.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	33.3 208.1%	0.0 0%
Month 4 (28 days post-dose 2)	25.0 125%	0.0 0%	0.0 0%	14.3 89.4%	0.0 0%
Month 9 (6 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

14. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	1.0	0.9	7.0	0.9
Month 4 (28 days post-dose 2)	5.8	2.2	1.0	4.9	1.1
Month 9 (6 months post-dose 2)	1.8	1.1	0.8	2.4	0.8
Month 15 (12 months post-dose 2)	1.5	1.4	0.8	2.1	0.8

15. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin A Antibody Seropositivity
Description	Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:100.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

16. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	5815	3536	6935	3408	2887
Month 1 (28 days post-dose 1)	6070	4781	7824	15919	3163
Month 4 (28 days post-dose 2)	23595	11095	7571	18079	2818
Month 15 (12 months post-dose 2)	10267	8460	5740	11856	2765

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk IgA (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1665
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 0.84 to 3.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgA (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9377
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.55 to 2.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3088
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

17. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	7.1 47.3%	0.0 0%	53.3 333.1%	0.0 0%
Month 4 (28 days post-dose 2)	62.5 312.5%	46.2 308%	0.0 0%	64.3 401.9%	0.0 0%
Month 15 (12 months post-dose 2)	14.3 71.5%	23.1 154%	0.0 0%	46.2 288.8%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4667
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	16.3
	Confidence Interval	(2-Sided) 95%; -19.85 to 48.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -34.76 to 32.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Serum) Humoral Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4495
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-18.1
	Confidence Interval	(2-Sided) 95%; -51.15 to 19.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) .
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	26.7 166.9%	0.0 0%
Month 4 (28 days post-dose 2)	18.8 94%	15.4 102.7%	0.0 0%	28.6 178.8%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	7.7 48.1%	0.0 0%

19. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgA Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin A (IgA) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgA antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]) . Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	1.4	1.1	4.7	1.1
Month 4 (28 days post-dose 2)	4.8	3.4	0.9	5.0	1.0
Month 15 (12 months post-dose 2)	1.8	2.6	0.6	3.1	1.0

20. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibody Seropositivity
Description	Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 [H6N1]) and the H1 stalk domain (strain A/California/04/2009 [H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

21. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Description	Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). The LLOQ for the assay was 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	48	49	63	58	43
Month 1 (28 days post-dose 1)	48	38	50	111	40
Month 4 (28 days post-dose 2)	153	94	40	138	37
Month 15 (12 months post-dose 2)	62	58	80	99	40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0928
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 0.94 to 2.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4198
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.77 to 2.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6754
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

22. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Description	Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	5.3 26.5%	0.0 0%	0.0 0%	20.0 125%	0.0 0%
Month 4 (28 days post-dose 2)	50.0 250%	30.8 205.3%	0.0 0%	35.7 223.1%	0.0 0%
Month 15 (12 months post-dose 2)	7.1 35.5%	15.4 102.7%	0.0 0%	15.4 96.3%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4515
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	19.2
	Confidence Interval	(2-Sided) 95%; -17.19 to 50.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4837
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	14.3
	Confidence Interval	(2-Sided) 95%; -21.22 to 46.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk MN (Serum) Assay: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -38.80 to 30.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Description	Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 ([H6N1]) and the H1 stalk domain (strain A/California/04/2009 ([H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	6.3 31.5%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

24. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk Neutralizing Antibodies
Description	Anti H1 hemagglutinin stalk neutralizing antibodies were quantified using a microneutralization (MN) assay using a virus that expresses a chimeric hemagglutinin that contains an exotic HA head domain (strain A/mallard/Sweden/81/2002 [H6N1]) and the H1 stalk domain (strain A/California/04/2009 [H1N1pandemic]) and an exotic neuraminidase, N5, for which humans are generally naïve (strain: A/mallard/Sweden/86/2003 [H12N5]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	0.8	0.8	1.9	0.9
Month 4 (28 days post-dose 2)	3.4	2.1	0.7	2.2	0.9
Month 15 (12 months post-dose 2)	1.2	1.3	0.5	1.5	0.9

25. Secondary Outcome

Title	Serum Antibody-dependent Cell-mediated Cytotoxicity (ADCC) to the H1 Hemagglutinin Stalk
Description	Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured in relative luciferase units (RLU) for serial dilutions of serum samples using a plate reader. ADCC activity was expressed by the area under the curve (AUC) of luminescence (RLU) per serial dilution (X-fold serial dilutions).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	321389	200649	486775	331849	109178
Month 1 (28 days post-dose 1)	322530	183017	693225	869805	103919
Month 4 (28 days post-dose 2)	1334738	366815	474913	863811	65371
Month 15 (12 months post-dose 2)	334076	353639	708455	508248	130882

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Serum cH6/1 - ADCC Activity: AUC at 28 Days Post-Boost
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	2.93
	Confidence Interval	(2-Sided) 95%; 1.56 to 7.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on log10 AUC, using the Hodges-Lehmann location parameter difference back-transformed to the original scale.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Serum cH6/1 - ADCC Activity: AUC at 28 Days Post-Boost
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2048
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 0.73 to 2.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on log10 AUC, using the Hodges-Lehmann location parameter difference back-transformed to the original scale.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Serum cH6/1 - ADCC Activity: AUC at 28 Days Post-Boost
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0392
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; 0.18 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Fold-Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
Description	Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at Baseline and each time point. The-per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	12	3	15	10
Month 1 (28 days post-dose 1)	0.9	1.1	1.2	2.4	1.0
Month 4 (28 days post-dose 2)	3.6	3.8	1.2	2.3	1.0
Month 15 (12 months post-dose 2)	1.8	1.8	1.25	1.9	0.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Serum cH6/1 - ADCC Activity: Fold Increase in AUC at 28 Days Post-Boost
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8243
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.14 to 4.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the Hodges-Lehmann location parameter difference on the log scale then back-transformed to the original scale.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Serum cH6/1 - ADCC Activity: Fold Increase in AUC at 28 Days Post-Boost
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2530
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95%; 0.67 to 6.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the Hodges-Lehmann location parameter difference on the log scale then back-transformed to the original scale.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Serum cH6/1 - ADCC Activity: Fold Increase in AUC at 28 Days Post-Boost
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5654
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.83
	Confidence Interval	(2-Sided) 95%; 0.47 to 39.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on the Hodges-Lehmann location parameter difference on the log scale then back-transformed to the original scale.

27. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
Description	Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at Baseline and each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	12	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	8.3 55.3%	0.0 0%	26.7 166.9%	10.0 100%
Month 4 (28 days post-dose 2)	50.0 250%	45.5 303.3%	0.0 0%	42.9 268.1%	10.0 100%
Month 15 (12 months post-dose 2)	28.6 143%	27.3 182%	0.0 0%	15.4 96.3%	0.0 0%

28. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum ADCC to the H1 Hemagglutinin Stalk
Description	Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response leading to lysis of antibody-coated target cells by immune effector cells and is triggered by the interaction between the Fc portion of an antibody and Fc-gamma receptors expressed on immune effector cells. This bioluminescent assay measured antibodies to a chimeric hemagglutinin (H6 head domain and H1 stalk domain) virus that mediate ADCC activity via the Fc-receptor. ADCC activity was measured by the area under the curve (AUC) of luminescence per serial dilution.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at Baseline and each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	12	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	8.3 55.3%	0. 0%	13.3 83.1%	0.0 0%
Month 4 (28 days post-dose 2)	31.3 156.5%	45.5 303.3%	0.0 0%	14.3 89.4%	0.0 0%
Month 15 (12 months post-dose 2)	14.3 71.5%	18.2 121.3%	0.0 0%	7.7 48.1%	0.0 0%

29. Secondary Outcome

Title	Percentage of Participants With Anti-H1 Hemagglutinin Stalk Salivary IgG Antibody Seropositivity
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	18	13	3	15	9
Baseline (pre-vaccination)	94.4 472%	84.6 564%	66.7 1334%	86.7 541.9%	88.9 889%
Month 1 (28 days post-dose 1)	94.4 472%	84.6 564%	100 2000%	100 625%	87.5 875%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	88.9 889%
Month 15 (12 months post-dose 2)	100 500%	91.7 611.3%	100 2000%	100 625%	88.9 889%

30. Secondary Outcome

Title	Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	18	13	3	15	9
Baseline (pre-vaccination)	40	43	21	55	45
Month 1 (28 days post-dose 1)	31	40	42	155	36
Month 4 (28 days post-dose 2)	161	131	15	233	61
Month 15 (12 months post-dose 2)	67	51	35	168	43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8830
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.45 to 3.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9238
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.33 to 2.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6926
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.26 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

31. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	18	13	3	15	9
Month 1 (28 days post-dose 1)	0.0 0%	7.7 51.3%	33.3 666%	40.0 250%	0.0 0%
Month 4 (28 days post-dose 2)	53.3 266.5%	41.7 278%	0.0 0%	57.1 356.9%	12.5 125%
Month 15 (12 months post-dose 2)	23.1 115.5%	9.1 60.7%	0.0 0%	33.3 208.1%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7036
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	11.7
	Confidence Interval	(2-Sided) 95%; -25.72 to 45.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -37.90 to 31.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk IgG (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6951
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-15.5
	Confidence Interval	(2-Sided) 95%; -49.56 to 22.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Salivary IgG
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	18	13	3	15	9
Month 1 (28 days post-dose 1)	0.0 0%	7.7 51.3%	0.0 0%	13.3 83.1%	0.0 0%
Month 4 (28 days post-dose 2)	20.0 100%	16.7 111.3%	0.0 0%	21.4 133.8%	12.5 125%
Month 15 (12 months post-dose 2)	7.7 38.5%	0.0 0%	0.0 0%	25.0 156.3%	0.0 0%

33. Secondary Outcome

Title	Mean Geometric Increase of Anti-H1 Hemagglutinin Stalk Salivary IgG Antibodies
Description	Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies in saliva against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	18	13	3	15	9
Month 1 (28 days post-dose 1)	0.7	0.9	2.0	2.8	0.8
Month 4 (28 days post-dose 2)	4.0	3.4	1.2	3.6	1.6
Month 15 (12 months post-dose 2)	2.0	1.5	1.2	2.8	0.8

34. Secondary Outcome

Title	Percentage of Participants With Anti-H1 Hemagglutinin Stalk Secretory IgA Antibody Seropositivity in Saliva
Description	Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:4.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

35. Secondary Outcome

Title	Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:4.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	86	102	58	221	155
Month 1 (28 days post-dose 1)	80	118	77	191	119
Month 4 (28 days post-dose 2)	93	136	47	201	115
Month 15 (12 months post-dose 2)	97	109	87	190	105

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3203
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.32 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5009
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.35 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9542
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.51 to 2.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

36. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	14	8
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	6.7 33.5%	8.3 55.3%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	28.6 143%	0.0 0%	0.0 0%	0.0 0%	12.5 125%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -30.62 to 23.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95%; -16.24 to 30.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Secretory IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4615
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	8.3
	Confidence Interval	(2-Sided) 95%; -19.94 to 36.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	14	8
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	6.7 33.5%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	14.3 71.5%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

38. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Secretory IgA in Saliva
Description	Anti-H1 hemagglutinin stalk secretory immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured secretory IgA antibodies antibodies (actively secreted in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	14	8
Month 1 (28 days post-dose 1)	0.9	1.1	1.3	0.8	0.7
Month 4 (28 days post-dose 2)	0.9	1.4	1.1	0.9	0.6
Month 15 (12 months post-dose 2)	1.1	1.1	1.6	0.9	0.7

39. Secondary Outcome

Title	Percentage of Participants With Anti-H1 Hemagglutinin Stalk Total IgA Antibody Seropositivity in Saliva
Description	Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	17	14	2	12	9
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

40. Secondary Outcome

Title	Geometric Mean Titer of Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). The LLOQ for the assay was 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	17	14	2	12	9
Baseline (pre-vaccination)	364	487	317	792	541
Month 1 (28 days post-dose 1)	369	685	280	849	321
Month 4 (28 days post-dose 2)	625	543	39	1149	672
Month 15 (12 months post-dose 2)	353	527	239	966	401

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9164
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95%; 0.38 to 3.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8642
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.21 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Adjusted GMT Ratio 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6545
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.18 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	GMT ratio computed after fitting an analysis of covariance (ANCOVA) model on the log10 transformed titers, including vaccine group as fixed effect and the pre-vaccination titer as covariate.

41. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	17	14	2	11	7
Month 1 (28 days post-dose 1)	12.5 62.5%	7.1 47.3%	0.0 0%	11.1 69.4%	14.3 143%
Month 4 (28 days post-dose 2)	30.8 154%	23.1 154%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	30.0 150%	23.1 154%	0.0 0%	16.7 104.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
	Comments	Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Seroresponse (>4-Fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; -27.10 to 40.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1045
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	30.8
	Confidence Interval	(2-Sided) 95%; -1.76 to 58.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV, Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant
	Comments	Comparison of Anti-H1 HA-stalk Total IgA (Saliva), Mucosal Response: Seroresponse (≥4-fold) Rate 28 Days Post-Boost Dose
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2292
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	23.1
	Confidence Interval	(2-Sided) 95%; -8.62 to 50.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

42. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	17	14	2	11	7
Month 1 (28 days post-dose 1)	6.3 31.5%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	7.7 38.5%	7.7 51.3%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	10.0 50%	0.0 0%	0.0 0%	0.0 0%

43. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Anti-H1 Hemagglutinin Stalk Total IgA Antibodies in Saliva
Description	Anti-H1 hemagglutinin stalk total immunoglobulin A (IgA) in saliva was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured total IgA antibodies (secreted through active and passive transfer processes in the mucosa) against the H1 stalk domain in saliva using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 [H6N1]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 [H1N1]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	17	14	2	11	7
Month 1 (28 days post-dose 1)	1.1	1.4	0.9	0.7	0.6
Month 4 (28 days post-dose 2)	1.7	1.2	0.7	1.1	0.9
Month 15 (12 months post-dose 2)	1.2	1.2	0.9	0.8

44. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H2 Full-length Hemagglutinin IgG Antibody Seropositivity
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 22.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

45. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	6973	6027	7354	7554	5597
Month 1 (28 days post-dose 1)	7079	6324	6757	67191	4971
Month 4 (28 days post-dose 2)	39171	13584	8348	41005	5493
Month 15 (12 months post-dose 2)	13289	10682	12289	26453	6283

46. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	80.0 500%	0.0 0%
Month 4 (28 days post-dose 2)	68.8 344%	7.7 51.3%	0.0 0%	71.4 446.3%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	7.7 51.3%	0.0 0%	46.2 288.8%	0.0 0%

47. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	53.3 333.1%	0.0 0%
Month 4 (28 days post-dose 2)	25.0 125%	0.0 0%	0.0 0%	14.3 89.4%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	7.7 51.3%	0.0 0%	0.0 0%	0.0 0%

48. Secondary Outcome

Title	Mean Geometric Increase of Serum Anti-H2 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H2, of which the stalk domain shares about 78% amino acid identity with the H1 vaccine stalk domain. Anti-H2 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on A/mallard/Netherlands/5/1999 (H2N9) HA. Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	1.0	0.9	8.9	0.9
Month 4 (28 days post-dose 2)	5.8	2.2	1.1	5.1	1.0
Month 15 (12 months post-dose 2)	2.0	1.8	1.3	3.3	1.1

49. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H9 Full-length Hemagglutinin IgG Antibody Seropositivity
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 31.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

50. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The LLOQ for the assay was 31 EU/mL.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	10613	8703	13257	10436	7981
Month 1 (28 days post-dose 1)	10610	8683	11641	37478	7477
Month 4 (28 days post-dose 2)	40587	16410	11081	41113	8244
Month 15 (12 months post-dose 2)	16809	12271	17996	24041	7593

51. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	40.0 250%	0.0 0%
Month 4 (28 days post-dose 2)	37.5 187.5%	7.7 51.3%	0.0 0%	50.0 312.5%	0.0 0%
Month 15 (12 months post-dose 2)	7.1 35.5%	7.7 51.3%	0.0 0%	23.1 144.4%	0.0 0%

52. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length(ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	6.7 41.9%	0.0 0%
Month 4 (28 days post-dose 2)	6.3 31.5%	0.0 0%	0.0 0%	7.1 44.4%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

53. Secondary Outcome

Title	Mean Geometric Increase of Serum Anti-H9 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin, subtype H9, the stalk domain of which shares about 59% amino acid identity with the H1 vaccine stalk domain. Anti-H9 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/chicken/Hong Kong/G9/1997 (H9N2) HA. Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	1.0	0.9	3.6	0.9
Month 4 (28 days post-dose 2)	3.8	1.9	0.9	3.7	1.0
Month 15 (12 months post-dose 2)	1.5	1.5	0.7	2.2	1.0

54. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H18 Full-length Hemagglutinin IgG Antibody Seropositivity
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 42.3.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

55. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	5764	5266	6142	7585	5315
Month 1 (28 days post-dose 1)	6030	5463	5238	30197	4977
Month 4 (28 days post-dose 2)	25400	9965	5178	30254	5702
Month 15 (12 months post-dose 2)	8478	6403	6783	14577	4747

56. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	40.0 250%	0.0 0%
Month 4 (28 days post-dose 2)	50.0 250%	15.4 102.7%	0.0 0%	50.0 312.5%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	7.7 51.3%	0.0 0%	23.1 144.4%	0.0 0%

57. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	13.3 83.1%	0.0 0%
Month 4 (28 days post-dose 2)	25.0 125%	0.0 0%	0.0 0%	14.3 89.4%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

58. Secondary Outcome

Title	Mean Geometric Increase of Serum Anti-H18 Full-length Hemagglutinin IgG Antibodies
Description	To determine antibody breadth, assays were performed to measure the induction of cross-reactive IgG antibodies to a Group 1 influenza A virus with a heterosubtypic hemagglutinin distantly related to the currently circulating influenza A/H1 viruses, subtype H18, the stalk domain of which shares about 65% amino acid identity with the H1 vaccine stalk domain. Anti-H18 full-length (ecto-domain) hemagglutinin IgG was quantified by ELISA using a recombinant antigen based on Strain A/flat-faced bat/Peru/033/10 (H18N11) HA. Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	1.0	0.9	4.0	0.9
Month 4 (28 days post-dose 2)	4.5	2.0	0.9	3.8	1.1
Month 15 (12 months post-dose 2)	1.4	1.3	0.9	1.8	0.9

59. Secondary Outcome

Title	Percentage of Participants With Serum Anti-Human H1N1 Virus Neutralizing Antibody Seropositivity
Description	This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

60. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). The LLOQ for the assay was 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	149	108	63	84	98
Month 1 (28 days post-dose 1)	172	113	50	175	80
Month 4 (28 days post-dose 2)	217	129	40	226	106
Month 15 (12 months post-dose 2)	113	129	80	136	130

61. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	5.3 26.5%	0.0 0%	0.0 0%	20.0 125%	0.0 0%
Month 4 (28 days post-dose 2)	25.0 125%	7.7 51.3%	0.0 0%	28.6 178.8%	10.0 100%
Month 15 (12 months post-dose 2)	0.0 0%	7.7 51.3%	0.0 0%	15.4 96.3%	10.0 100%

62. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	6.3 31.5%	0.0 0%	0.0 0%	7.1 44.4%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

63. Secondary Outcome

Title	Mean Geometric Increase of Serum Anti-Human H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of antibodies against the currently circulating human H1N1 isolate which is similar to the stalk used in study vaccines. Anti-human H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Singapore/GP1908/2015 (IVR-180). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.2	1.1	0.8	2.1	0.8
Month 4 (28 days post-dose 2)	1.8	1.3	1.0	2.4	1.1
Month 15 (12 months post-dose 2)	1.0	1.3	1.0	1.6	1.3

64. Secondary Outcome

Title	Percentage of Participants With Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibody Seropositivity
Description	This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

65. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). The LLOQ for the assay was 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	54	46	63	73	61
Month 1 (28 days post-dose 1)	56	54	63	127	46
Month 4 (28 days post-dose 2)	141	72	40	195	57
Month 15 (12 months post-dose 2)	69	58	80	94	70

66. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	7.1 47.3%	0.0 0%	20.0 125%	0.0 0%
Month 4 (28 days post-dose 2)	37.5 187.5%	7.7 51.3%	0.0 0%	28.6 178.8%	0.0 0%
Month 15 (12 months post-dose 2)	14.3 71.5%	15.4 102.7%	0.0 0%	7.7 48.1%	0.0 0%

67. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

68. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Serum Anti-Avian-Swine H1N1 Virus Neutralizing Antibodies
Description	This assay was performed to measure the neutralizing potential of cross-reactive antibodies to a Group 1 influenza against an H1N1 virus isolate that currently circulates in animals and is antigenically different from current human isolates. Anti-avian-swine H1N1 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using Strain A/Swine/Jiangsu/40/2011 (asH1N1). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	1.2	1.0	1.7	0.8
Month 4 (28 days post-dose 2)	2.8	1.6	1.0	2.4	0.9
Month 15 (12 months post-dose 2)	1.4	1.3	1.0	1.3	1.1

69. Secondary Outcome

Title	Percentage of Participants With Serum Anti-H5N8 Virus Neutralizing Antibody Seropositivity
Description	This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on Puerto Rico (PR)/8 for 6 genes with 2 surface proteins: HA and neuraminidase (NA) from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). Seropositivity rate was defined as the percentage of participants with an antibody titer of ≥ 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 1 (28 days post-dose 1)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 4 (28 days post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%
Month 15 (12 months post-dose 2)	100 500%	100 666.7%	100 2000%	100 625%	100 1000%

70. Secondary Outcome

Title	Geometric Mean Titer of Serum Anti-H5N8 Virus Neutralizing Antibodies
Description	This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). The LLOQ for the assay was 1:10.
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Baseline (pre-vaccination)	37	30	40	35	28
Month 1 (28 days post-dose 1)	36	27	50	55	26
Month 4 (28 days post-dose 2)	62	47	57	66	30
Month 15 (12 months post-dose 2)	42	34	20	55	30

71. Secondary Outcome

Title	Percentage of Participants With a ≥ 4-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies
Description	This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	6.7 41.9%	0.0 0%
Month 4 (28 days post-dose 2)	12.5 62.5%	15.4 102.7%	0.0 0%	14.3 89.4%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	15.4 102.7%	0.0 0%	0.0 0%	0.0 0%

72. Secondary Outcome

Title	Percentage of Participants With a ≥ 10-fold Increase in Serum Anti-H5N8 Virus Neutralizing Antibodies
Description	This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 4 (28 days post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Month 15 (12 months post-dose 2)	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

73. Secondary Outcome

Title	Mean Geometric Increase From Baseline in Serum Anti-H5N8 Virus Neutralizing Antibodies
Description	This assay was performed to measure the induction of antibodies reactive against the head domain of a group 1 influenza virus with a heterosubtypic hemagglutinin from a recent avian influenza virus. Anti-H5N8 virus neutralizing antibodies were quantified using a microneutralization (MN) assay using a reverse genetics (RG) reassortant virus based on PR8 for 6 genes with 2 surface proteins: HA and NA from A/Gyrfalcon/Washington/41088-6/2014 (H5N8). Mean geometric increase represents the fold-rise in antibody titer from Baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).
Time Frame	Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), and Month 15 (12 months post-dose 2)

Outcome Measure Data

Analysis Population Description

Participants in the per-protocol population with available data at each time point. The per-protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV	Group 3: Placebo	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant	Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Measure Participants	19	14	3	15	10
Month 1 (28 days post-dose 1)	1.0	0.9	1.3	1.6	0.9
Month 4 (28 days post-dose 2)	1.8	1.6	1.4	1.9	1.1
Month 15 (12 months post-dose 2)	1.1	1.2	1.0	1.5	1.1

Adverse Events

Time Frame	All-cause mortality and serious adverse events were recorded through the end of study, 588 days (21 months). Other adverse events were collected through 28 days after each vaccination (Days 1 to 28 and Days 85 to 113)
Arm/Group Title	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant		Group 2: cH8/1N1 LAIV and cH5/1N1 IIV		Group 3: Placebo		Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant		Group 5: Placebo
Arm/Group Description	Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.		Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.		Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.		Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.		Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
All Cause Mortality
	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant		Group 2: cH8/1N1 LAIV and cH5/1N1 IIV		Group 3: Placebo		Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant		Group 5: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/14 (0%)		1/3 (33.3%)		0/15 (0%)		0/10 (0%)
Serious Adverse Events
	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant		Group 2: cH8/1N1 LAIV and cH5/1N1 IIV		Group 3: Placebo		Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant		Group 5: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/14 (0%)		1/3 (33.3%)		0/15 (0%)		2/10 (20%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	0/19 (0%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		1/10 (10%)
Injury, poisoning and procedural complications
Road traffic accident	0/19 (0%)		0/14 (0%)		1/3 (33.3%)		0/15 (0%)		0/10 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/19 (0%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant		Group 2: cH8/1N1 LAIV and cH5/1N1 IIV		Group 3: Placebo		Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant		Group 5: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/19 (52.6%)		8/14 (57.1%)		1/3 (33.3%)		6/15 (40%)		5/10 (50%)
Blood and lymphatic system disorders
Lymph node pain	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Lymphadenopathy	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		1/15 (6.7%)		0/10 (0%)
Eye disorders
Photophobia	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Vision blurred	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Gastrointestinal disorders
Toothache	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Vomiting	0/19 (0%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		1/10 (10%)
General disorders
Chest pain	0/19 (0%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		1/10 (10%)
Infections and infestations
Bacterial vaginosis	0/19 (0%)		1/14 (7.1%)		0/3 (0%)		1/15 (6.7%)		0/10 (0%)
Cervicitis	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Gastroenteritis	1/19 (5.3%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Gastroenteritis viral	1/19 (5.3%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Respiratory tract infection viral	0/19 (0%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Upper respiratory tract infection	1/19 (5.3%)		2/14 (14.3%)		0/3 (0%)		2/15 (13.3%)		0/10 (0%)
Viral upper respiratory tract infection	0/19 (0%)		2/14 (14.3%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Injury, poisoning and procedural complications
Foot fracture	0/19 (0%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/19 (0%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Back pain	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Musculoskeletal pain	0/19 (0%)		0/14 (0%)		1/3 (33.3%)		0/15 (0%)		0/10 (0%)
Myalgia	1/19 (5.3%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		1/10 (10%)
Nervous system disorders
Headache	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Presyncope	0/19 (0%)		0/14 (0%)		0/3 (0%)		1/15 (6.7%)		0/10 (0%)
Reproductive system and breast disorders
Vulvovaginal pruritis	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Epistaxis	2/19 (10.5%)		2/14 (14.3%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Nasal congestion	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Nasal discomfort	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Nasal mucosal disorder	0/19 (0%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Oropharyngeal pain	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		2/10 (20%)
Pharyngeal erythema	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Rhinitis allergic	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Rhinorrhoea	0/19 (0%)		0/14 (0%)		0/3 (0%)		1/15 (6.7%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/19 (0%)		1/14 (7.1%)		0/3 (0%)		1/15 (6.7%)		0/10 (0%)
Erythema	0/19 (0%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Hyperhidrosis	1/19 (5.3%)		1/14 (7.1%)		0/3 (0%)		0/15 (0%)		0/10 (0%)
Pruritis	1/19 (5.3%)		0/14 (0%)		0/3 (0%)		0/15 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.