Flublok or Fluzone With Advax-CpG55.2 or AF03

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03945825
• Collaborator: (none)
• Enrollment: 241
• Locations: 8
• Arms: 6
• Actual Duration (Months): 15.3
• Patients Per Site: 30.1
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant.

Condition or Disease	Intervention/Treatment	Phase
Influenza; Influenza Immunisation	Drug: AF03; Biological: Delta Inulin-CpG55.2; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine	Phase 1

Detailed Description

This is a Phase I, randomized, double blinded, clinical trial in up to 240 males and non-pregnant females, 18-45 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of either the 2018/2019 seasonal Fluzone or Flublok Quadrivalent Influenza Vaccine (QIV) manufactured by Sanofi Pasteur (SP) given without adjuvant or with one of two adjuvant formulations, AF03 or Advax-CpG55.2. Subjects will be stratified by prior receipt of licensed, seasonal influenza vaccine (defined as receipt of at least one of the 2017/2018 and/or 2018/2019 influenza vaccines) and will be randomly assigned to 1 of 6 treatment arms to receive a single dose of one of the two seasonal 2018/2019 QIV vaccine formulations with or without one of the two adjuvants (Day 1). On approximately Day 90, each subject will receive a single dose of the seasonal 2019/2020 QIV. Groups 1, 2 and 3 will receive 2019/2020 Fluzone QIV and Groups 4, 5 and 6 will receive 2019/2020 Flublok QIV. Eight Vaccine and Treatment Evaluation Unit (VTEU) sites will be included in the study. Study duration is approximately 18 months, and subject participation duration is 12 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) antibody responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 3) to assess the serum neuraminidase inhibition antibody (NAI) responses by enzyme-linked lectin assay (ELLA) against NA antigens in the 2018/2019 QIV from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess the influenza neutralizing (Neut) antibody titer responses against 2018/2019 QIV strains from baseline (Day 1) to approximately Day 29 after receipt of 2018/2019 Fluzone and Flublok with and without AF03 or Advax- CpG55.2 adjuvant. The secondary objectives of this study are: 1) to assess protocol specified adverse events of special interest (AESI), medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) that occur after receipt of study product; 2) to assess the HAI, Neut and NAI ELLA responses to the 2019/2020 QIV strains prior to (Day 1) and approximately 28 days after vaccination with the 2019/2020 QIV in all study groups; 3) to assess the HAI antibody responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after receipt of 2018/2019 Fluzone or Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 4) to assess NAI ELLA responses against heterologous N1 and N2 NA antigens from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone with and without AF03 or Advax-CpG55.2 adjuvant; 5) to assess the influenza neutralizing (Neut) antibody titer responses against heterologous influenza A/H1 and H3 strains from baseline (Day 1) to approximately Days 8, 29, 57, 90 and 118 after administration of 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant; 6) to assess the longitudinal kinetics and durability of the HAI, NAI, and Neut responses against the 2018/2019 QIV strains on approximately Days 8, 57, 90 and 118 following receipt of the 2018/2019 Fluzone and Flublok with and without AF03 or Advax-CpG55.2 adjuvant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 241 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase I Study to Assess the Safety, Reactogenicity and Immunogenicity of Two Quadrivalent Seasonal Influenza Vaccines (Fluzone(R) or Flublok(R)) With or Without One of Two Adjuvants (AF03 or Advax-CpG55.2) in Healthy Adults 18-45 Years of Age
• Actual Study Start Date: Jun 10, 2019
• Actual Primary Completion Date: Sep 18, 2020
• Actual Study Completion Date: Sep 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40	Biological: Influenza Virus Quadrivalent Inactivated Vaccine; 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental: Group 2 0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90, n=40	Drug: AF03; A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether; Biological: Influenza Virus Quadrivalent Inactivated Vaccine; 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental: Group 3 0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90, n=40	Biological: Delta Inulin-CpG55.2; A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd); Biological: Influenza Virus Quadrivalent Inactivated Vaccine; 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval
Experimental: Group 4 0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40	Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine; 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Experimental: Group 5 0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40	Drug: AF03; A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether; Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine; 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Experimental: Group 6 0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90, n=40	Biological: Delta Inulin-CpG55.2; A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd); Biological: Quadrivalent Recombinant Seasonal Influenza Vaccine; 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting Local and Systemic Solicited Reactogenicity Events Post First Vaccination [Day 1 through Day 8]

   Local adverse events (AEs) solicited on a memory aid provided to participants included Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with daily activities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (any measured value >0mm). Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the local or systemic AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.

2. Number of Participants Reporting Serious and Non-serious Adverse Events (AE) Through Day 29 [Day 1 through Day 29]

   Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through 28 days after the first study vaccination while serious adverse events (SAEs) were collected at follow up visits through approximately 12 months after the first study vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).

3. Number of Participants Reporting Serious Adverse Events (SAEs) [Day 1 through Day 365]

   SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. All SAEs were reported from time of first study vaccination through approximately 12 months after the first study vaccination.

4. Number of Participants Reporting Clinical Safety Laboratory Adverse Events (AEs) Post First Vaccination [Day 1 through Day 8]

   Laboratory parameters include white blood cells (WBC), hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, Gamma-Glutamyl Transferase (GGT), alkaline phosphatase (ALP), amylase, lipase, and creatinine. Thresholds for adverse events were considered WBC of 3.90 x10^3/uL or lower or 10.60 x10^3/uL or higher; hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/uL or below or 416 x10^3/uL or greater when using EDTA tubes or platelets 124 x10^3/uL or below or 550 x10^3/uL or greater when using Citrate tubes; ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); AST 37 IU/L or greater (female) or 44 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; GGT 33 IU/L or greater (female) or 50 IU/L or greater (male); ALP 116 IU/L or greater; amylase 122 IU/L or greater; lipase 61 IU/L or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male).

5. Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 1, Day 29]

   Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.

6. Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 1, Day 29]

   Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

7. Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 29]

   Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

8. Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 1, Day 29]

   Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.

9. Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 29]

   Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

10. Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 1, Day 29]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.

11. Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 1, Day 29]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

12. Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 29]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 29.

13. Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 29]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

14. Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 1, Day 29]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.

15. Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 1, Day 29]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

16. Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 29]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

17. Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 1, Day 29]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab.

18. Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 29]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

Secondary Outcome Measures

1. Number of Participants Reporting Protocol Specified Adverse Events of Special Interest (AESIs) [Day 1 through Day 365]

   Participants were queried at each visit for the occurrence of adverse events of special interest (AESIs) through approximately 12 months following the first study vaccination. AESIs include reports of tearing, dry mouth, and dry eyes.

2. Number of Participants Reporting Medically-Attended Adverse Events (MAAEs), New-Onset Chronic Medical Conditions (NOCMCs), and Potentially Immune-Mediated Medical Conditions (PIMMCs) [Day 1 through Day 365]

   Participants were queried at each visit for the occurrence of medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) through approximately 12 months following the first study vaccination.

3. Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 90 through Day 118]

   Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination.

4. Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 90 through Day 118]

   Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

5. Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 118]

   Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-second vaccination titer < 1:10 and a post- second vaccination titer >= 1:40 or a pre-second vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

6. Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 90 through Day 118]

   Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.

7. Geometric Mean Fold Rise in Hemagglutination Inhibition (HAI) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 90 through Day 118]

   Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises at Day 118 were calculated as the Day 118 titer divided by the Day 90 titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

8. Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms [Day 90 through Day 118]

   Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination.

9. Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms [Day 90 through Day 118]

   Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. The unadjuvanted Fluzone study arm is considered a reference group for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

10. Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms [Day 118]

    Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 90 through Day 118.

11. Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms [Day 118]

    Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises at Day 118 were calculated as the Day 118 titer divided by the Day 90 titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

12. Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 90 through Day 118]

    Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination.

13. Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 90 through Day 118]

    Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

14. Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 118]

    Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-second vaccination titer < 1:10 and a post-second vaccination titer >= 1:40 or a pre-second vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

15. Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains [Day 118]

    Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises at Day 118 were calculated as the Day 118 titer divided by the Day 90 titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

16. Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination.

17. Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

18. Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

19. Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.

20. Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

21. Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination.

22. Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. The unadjuvanted Fluzone study arm is considered a reference group for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

23. Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 8, 57, 90, and 118.

24. Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

25. Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination.

26. Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

27. Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

28. Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab.

29. Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains [Day 8, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 8 (or Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

30. Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against Heterologous H1 and H3 Influenza Strains [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 post first study vaccination.

31. Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against Heterologous H1 and H3 Influenza Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms was calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

32. Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against Heterologous H1 and H3 Influenza Strains [Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

33. Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against Heterologous H1 and H3 Influenza Strains [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.

34. Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against Heterologous H1 and H3 Influenza Strains [Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 29, Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

35. Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination.

36. Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against Heterologous N1 and N2 Neuraminidase (NA) Antigens Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. The unadjuvanted Fluzone study arm is considered a reference group for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

37. Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms [Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 8, 29, 57, 90, and 118.

38. Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms [Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 29, Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

39. Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against Heterologous H1 and H3 Influenza Strains [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination.

40. Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against Heterologous H1 and H3 Influenza Strains Between Adjuvanted and Unadjuvanted Study Arms [Day 1, Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.

41. Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against Heterologous H1 and H3 Influenza Strains [Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.

42. Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against Heterologous H1 and H3 Influenza Strains [Day 8, Day 29, Day 57, Day 90, Day 118]

    Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 8 (or Day 29, Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Provide written informed consent prior to initiation of any study procedures.

2. Are able to understand and comply with planned study procedures and be available for all study visits.

3. Must agree to the collection of venous blood per protocol.

4. Are males or non-pregnant females, 18 to 45 years of age, inclusive at time of enrollment.

5. Are in good health*. *As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose or in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low dose topical, corticosteroids as outlined in the Subject Exclusion Criteria as well as herbals, vitamins and supplements are permitted.

6. Oral temperature is less than 100.0 degrees Fahrenheit.

7. Pulse is 47 to 100 beats per minute, inclusive.

8. Systolic blood pressure is 85 to 140 mmHg, inclusive.

9. Diastolic blood pressure is 55 to 90 mmHg, inclusive.

10. Screening laboratories (Erythrocyte Sedimentation Rate (ESR), White Blood Cells (WBC), Hemoglobin (Hgb), Platelets (PLTs), Alanine Aminotransferase (ALT), Total Bilirubin (T. Bili), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Alkaline Phosphatase (ALP) serum lipase, serum amylase and Creatinine (Cr)) are within acceptable parameters*.

*ESR must be below 30 mm/hr; WBC >3.90 K/MM3 and <10.60 K/MM3; Hgb >/= 11.5 g/dl (women) or >/= 12.5 g/dl (men); PLTs (EDTA) 140-415 K/MM3; PLTs (Citrate) 125-325 K/MM3 ALT </= 43 U/L (women) or </= 60 U/L (men); T Bili </=1.20 mg/dl; Cr < 1.1 mg/dl (women) or < 1.4 mg/dl (men); AST 10-36 U/L (women) or 10-43 U/L (men); GGT 5--32 U/L (women) or 10-49 U/L (men); ALP 30-115 U/L (women) or 43-115 U/L (men); lipase 13-60 U/L; amylase (Total) 35-121 U/L, for subjects to qualify for randomization and vaccination.

1. Women of childbearing potential* must use an acceptable contraception method** from at least 30 days before the first study vaccination until 60 days after the second study vaccination.

*Not sterilized via bilateral oophorectomy, tubal ligation/ salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year has passed since the last menses if menopausal.

• Includes non-male sexual relationships, full abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more and shown to be azoospermic prior to the subject receiving the study vaccination, barrier methods such as condoms or diaphragms/cervical cap with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").

1. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to the first study vaccination.

2. For a woman with potential to become pregnant, she understands that in the event of pregnancy during the study she will be approached to enroll in the Sanofi Pregnancy Registry.

3. Must agree to have residual specimens (i.e. residual/excess of per protocol specifications).

Exclusion Criteria:

1. Have an acute illness*, as determined by the site Principal Investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination.

*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.

1. Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation*.

*Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.

1. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.

2. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.

3. Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.

4. Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.

5. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.

6. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.

7. Have a history of Guillain-Barré Syndrome (GBS).

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

9. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).

10. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

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

*As determined by the site PI or appropriate sub-investigator.

1. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination.

2. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.

3. Have taken high-dose inhaled corticosteroids* within 30 days prior to study vaccination.

*High-dose defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.

1. Received or plan to receive a licensed, live vaccine (excluding all licensed, seasonal LAIVs) within 30 days before or after the study vaccination.

2. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed, seasonal IIVs) within 14 days before or after each study vaccination.

3. Have received any 2018/2019 seasonal influenza vaccine within the 6 months prior to enrollment.

4. Plans to receive any 2019/2020 seasonal influenza vaccine within approximately 90 days of receipt of the first study vaccination.

5. Have a known history of documented influenza infection within the past 6 months.

6. Received immunoglobulin or other blood products (except Rho D immunoglobulin) within 90 days prior to study vaccination.

7. Received an experimental agent* within 30 days prior to the study vaccination or expect to receive another experimental agent* during the trial-reporting period*.

*Including vaccine, drug, biologic, device, blood product, or medication.

**Other than from participation in this trial.

***Approximately 12 months after the first study vaccination.

1. Are participating or plan to participate in another clinical trial with an interventional agent* that will be received during the trial-reporting period**.

*Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.

**Approximately 12 months after the first study vaccination.

1. Female subjects who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the last study vaccination.

2. Plan to travel outside the US (continental US, Hawaii and Alaska) from the time of study vaccination through approximately 90 days after the first study vaccination.

3. Planning to donate blood within 4 months following first vaccination.

Exclusion Criteria for Second Study Vaccination:

All study participants will be expected to receive the second study vaccination except under the circumstances listed below. The second study vaccination will not be administered to a subject if any of the following criteria are met:

• Meets the contraindication on the package insert to receipt of licensed influenza vaccine.

• As deemed necessary by the site principal investigator or appropriate sub-investigator for noncompliance or other reasons.

• Subject refusal of further study vaccination.

• Withdrawal of consent.

• Subject is lost to follow-up.

• Termination of this trial.

• New information becomes available that makes further participation unsafe.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory Children's Center - Pediatric Infectious Diseases	Atlanta	Georgia	United States	30322-1014
2	University of Iowa - Vaccine Research and Education Unit	Iowa City	Iowa	United States	52242-2600
3	University of Maryland Baltimore - School of Medicine - Medicine	Baltimore	Maryland	United States	21201-1509
4	Saint Louis University - Center for Vaccine Development	Saint Louis	Missouri	United States	63104-1015
5	Duke Human Vaccine Institute - Duke Vaccine and Trials Unit	Durham	North Carolina	United States	27704
6	Cincinnati Children's Hospital Medical Center - Infectious Diseases	Cincinnati	Ohio	United States	45229-3039
7	Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center	Nashville	Tennessee	United States	37232-2573
8	Baylor College of Medicine - Molecular Virology and Microbiology	Houston	Texas	United States	77030-3411

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 1, 2021
• Statistical Analysis Plan - May 4, 2021
• Informed Consent Form - Jun 4, 2019

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03945825
• Other Study ID Numbers: 18-0011; HHSN272201300015I
• First Posted: May 10, 2019
• Last Update Posted: Jan 3, 2022
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Immunogenicity; Influenza; Influenza Vaccine; Phase 1; Quadrivalent; Safety
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Participants were healthy males and non-pregnant females aged 18 to 45 years old recruited from existing volunteer populations and from the communities at large around the clinical sites. Participants were enrolled between 18JUN2019 and 27AUG2019.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90. Influenza Virus Quadrivalent Inactivated Vaccine: unadjuvanted 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90. AF03: A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether Influenza Virus Quadrivalent Inactivated Vaccine: 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL 2019/2020 of Fluzone QIV intramuscular injection on Day 90. Delta Inulin-CpG55.2 (referred to as CpG55): A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd) Influenza Virus Quadrivalent Inactivated Vaccine: 2018/2019 Fluzone QIV and 2019/2020 Fluzone QIV vaccines will be given with 90 days interval	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. Quadrivalent Recombinant Seasonal Influenza Vaccine: unadjuvanted 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. AF03: A squalene-in-PBS emulsion stabilized by nonionic surfactants, sorbitan oleate and macrogol cetostearyl ether Quadrivalent Recombinant Seasonal Influenza Vaccine: 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. Delta Inulin-CpG55.2 (referred to as CpG55): A combination adjuvant supplied as two separate components, Delta Inulin (Sypharma Pty Ltd.) and CpG55.2 (Nikko Denka Avecia and Sypharma Pty Ltd) Quadrivalent Recombinant Seasonal Influenza Vaccine: 2018/2019 Flublok QIV and 2019/2020 Flublok QIV vaccines will be given with 90 days interval
Period Title: Overall Study
STARTED	41	37	40	41	39	43
COMPLETED	39	32	39	39	36	40
NOT COMPLETED	2	5	1	2	3	3

Baseline Characteristics

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55	Total
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	Total of all reporting groups
Overall Participants	41	37	40	41	39	43	241
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	41 100%	37 100%	40 100%	41 100%	39 100%	43 100%	241 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.7 (7.2)	29.6 (6.2)	28.2 (7.0)	30.2 (7.6)	29.7 (6.8)	28.7 (6.5)	29.5 (6.9)
Sex: Female, Male (Count of Participants)
Female	22 53.7%	26 70.3%	28 70%	27 65.9%	23 59%	26 60.5%	152 63.1%
Male	19 46.3%	11 29.7%	12 30%	14 34.1%	16 41%	17 39.5%	89 36.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.4%	4 10.8%	3 7.5%	7 17.1%	5 12.8%	3 7%	23 9.5%
Not Hispanic or Latino	40 97.6%	33 89.2%	36 90%	34 82.9%	34 87.2%	40 93%	217 90%
Unknown or Not Reported	0 0%	0 0%	1 2.5%	0 0%	0 0%	0 0%	1 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 2.4%	0 0%	0 0%	1 0.4%
Asian	1 2.4%	2 5.4%	4 10%	5 12.2%	5 12.8%	5 11.6%	22 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 17.1%	4 10.8%	2 5%	7 17.1%	8 20.5%	2 4.7%	30 12.4%
White	33 80.5%	28 75.7%	32 80%	26 63.4%	24 61.5%	34 79.1%	177 73.4%
More than one race	0 0%	2 5.4%	2 5%	1 2.4%	2 5.1%	2 4.7%	9 3.7%
Unknown or Not Reported	0 0%	1 2.7%	0 0%	1 2.4%	0 0%	0 0%	2 0.8%
Region of Enrollment (participants) [Number]
United States	41 100%	37 100%	40 100%	41 100%	39 100%	43 100%	241 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.73 (5.37)	26.87 (6.29)	24.82 (4.64)	26.91 (6.55)	26.25 (6.81)	25.79 (5.67)	26.22 (5.91)
Prior Seasonal Influenza Vaccination (Count of Participants)
Either 2017-2018 or 2018-2019	36 87.8%	29 78.4%	32 80%	32 78%	30 76.9%	36 83.7%	195 80.9%
Neither 2017-2018 or 2018-2019	5 12.2%	7 18.9%	8 20%	8 19.5%	9 23.1%	7 16.3%	44 18.3%
Unknown	0 0%	1 2.7%	0 0%	1 2.4%	0 0%	0 0%	2 0.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Local and Systemic Solicited Reactogenicity Events Post First Vaccination
Description	Local adverse events (AEs) solicited on a memory aid provided to participants included Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with daily activities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (any measured value >0mm). Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the local or systemic AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.
Time Frame	Day 1 through Day 8

Outcome Measure Data

Analysis Population Description

The Safety Analysis population includes all participants who received the first study vaccination. Analyses for the safety population are based on vaccine actually received. One participant randomized to Flublok + AF03 group received Flublok due to a pharmacy error and is analyzed in the Flublok group.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	42	37	43
Any Systemic Symptom	24 58.5%	25 67.6%	23 57.5%	23 56.1%	18 46.2%	26 60.5%
Any Local Symptom	35 85.4%	36 97.3%	40 100%	32 78%	33 84.6%	43 100%

2. Primary Outcome

Title	Number of Participants Reporting Serious and Non-serious Adverse Events (AE) Through Day 29
Description	Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through 28 days after the first study vaccination while serious adverse events (SAEs) were collected at follow up visits through approximately 12 months after the first study vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The Safety Analysis population includes all participants who received the first study vaccination. Analyses for the safety population are based on vaccine actually received. One participant randomized to Flublok + AF03 group received Flublok due to a pharmacy error and is analyzed in the Flublok group.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	42	37	43
AEs	12 29.3%	11 29.7%	8 20%	14 34.1%	10 25.6%	15 34.9%
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants Reporting Serious Adverse Events (SAEs)
Description	SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. All SAEs were reported from time of first study vaccination through approximately 12 months after the first study vaccination.
Time Frame	Day 1 through Day 365

Outcome Measure Data

Analysis Population Description

The Safety Analysis population includes all participants who received the first study vaccination. Analyses for the safety population are based on vaccine actually received. One participant randomized to Flublok + AF03 group received Flublok due to a pharmacy error and is analyzed in the Flublok group.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	42	37	43
Count of Participants [Participants]	0 0%	1 2.7%	0 0%	0 0%	0 0%	1 2.3%

4. Primary Outcome

Title	Number of Participants Reporting Clinical Safety Laboratory Adverse Events (AEs) Post First Vaccination
Description	Laboratory parameters include white blood cells (WBC), hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, Gamma-Glutamyl Transferase (GGT), alkaline phosphatase (ALP), amylase, lipase, and creatinine. Thresholds for adverse events were considered WBC of 3.90 x10^3/uL or lower or 10.60 x10^3/uL or higher; hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/uL or below or 416 x10^3/uL or greater when using EDTA tubes or platelets 124 x10^3/uL or below or 550 x10^3/uL or greater when using Citrate tubes; ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); AST 37 IU/L or greater (female) or 44 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; GGT 33 IU/L or greater (female) or 50 IU/L or greater (male); ALP 116 IU/L or greater; amylase 122 IU/L or greater; lipase 61 IU/L or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male).
Time Frame	Day 1 through Day 8

Outcome Measure Data

Analysis Population Description

The Safety Analysis population includes all participants who received the first study vaccination. Analyses for the safety population are based on vaccine actually received. One participant randomized to Flublok + AF03 group received Flublok due to a pharmacy error and is analyzed in the Flublok group.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	42	37	43
WBCs	6 14.6%	2 5.4%	3 7.5%	2 4.9%	3 7.7%	0 0%
Hemoglobin	1 2.4%	1 2.7%	2 5%	3 7.3%	0 0%	0 0%
Platelets	0 0%	0 0%	0 0%	4 9.8%	0 0%	0 0%
ALT	1 2.4%	1 2.7%	0 0%	1 2.4%	1 2.6%	1 2.3%
AST	0 0%	1 2.7%	0 0%	1 2.4%	2 5.1%	1 2.3%
Bilirubin	0 0%	0 0%	1 2.5%	0 0%	1 2.6%	0 0%
GGT	2 4.9%	0 0%	0 0%	0 0%	0 0%	2 4.7%
ALP	0 0%	0 0%	0 0%	0 0%	1 2.6%	1 2.3%
Amylase	1 2.4%	0 0%	1 2.5%	0 0%	0 0%	0 0%
Lipase	0 0%	1 2.7%	1 2.5%	0 0%	0 0%	0 0%
Creatinine	1 2.4%	0 0%	0 0%	0 0%	0 0%	1 2.3%

5. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	114.1	193.0	96.8	164.1	129.7	108.6
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 1	140.9	149.8	120.2	248.3	107.1	131.3
A/Michigan/45/2015 X-275 (H1N1) - Day 1	242.1	196.6	174.5	296.6	186.8	237.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	366.3	478.7	489.3	618.7	331.9	390.1
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	270.2	538.2	340.5	634.5	516.0	492.5
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 29	423.0	456.9	349.7	515.4	416.0	388.7
A/Michigan/45/2015 X-275 (H1N1) - Day 29	488.3	474.9	365.6	680.0	722.9	522.5
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	952.2	1356.1	1081.1	1645.6	1280.0	1280.0

6. Primary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	1.7	0.8	0.8	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 1	1.1	0.9	0.4	0.5
A/Michigan/45/2015 X-275 (H1N1) - Day 1	0.8	0.7	0.6	0.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	1.3	1.3	0.5	0.6
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	2.0	1.3	0.8	0.8
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 29	1.1	0.8	0.8	0.8
A/Michigan/45/2015 X-275 (H1N1) - Day 29	1.0	0.7	1.1	0.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	1.4	1.1	0.8	0.8

7. Primary Outcome

Title	Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	36	39	40	37	41
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2)	27 65.9%	33 89.2%	36 90%	45 109.8%	46 117.9%	56 130.2%
B/Maryland/15/2016 BX-69A (B Victoria lineage)	29 70.7%	36 97.3%	31 77.5%	23 56.1%	41 105.1%	32 74.4%
A/Michigan/45/2015 X-275 (H1N1)	24 58.5%	19 51.4%	18 45%	23 56.1%	46 117.9%	32 74.4%
B/Phuket/3073/2013 (B Yamagata lineage)	24 58.5%	25 67.6%	23 57.5%	28 68.3%	30 76.9%	34 79.1%

8. Primary Outcome

Title	Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	85 207.3%	95 256.8%	75 187.5%	93 226.8%	76 194.9%	88 204.7%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 1	80 195.1%	89 240.5%	80 200%	90 219.5%	79 202.6%	90 209.3%
A/Michigan/45/2015 X-275 (H1N1) - Day 1	93 226.8%	95 256.8%	88 220%	93 226.8%	89 228.2%	95 220.9%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	98 239%	95 256.8%	100 250%	95 231.7%	92 235.9%	100 232.6%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 29	100 243.9%	100 270.3%	97 242.5%	100 243.9%	97 248.7%	100 232.6%
A/Michigan/45/2015 X-275 (H1N1) - Day 29	100 243.9%	100 270.3%	97 242.5%	98 239%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%

9. Primary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	36	39	40	37	41
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2)	2.4	2.6	3.6	3.8	3.8	4.3
B/Maryland/15/2016 BX-69A (B Victoria lineage)	3.0	3.2	2.9	2.1	3.7	2.9
A/Michigan/45/2015 X-275 (H1N1)	2.0	2.3	2.2	2.1	3.7	2.1
B/Phuket/3073/2013 (B Yamagata lineage)	2.6	2.7	2.3	2.6	4.0	3.2

10. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	123.1	116.4	91.9	140.9	129.7	105.9
B/Colorado/06/2017 (B Victoria lineage) - Day 1	178.6	211.9	213.0	256.9	226.3	166.7
A/Michigan/45/2015 X-275 (H1N1) - Day 1	118.0	108.0	96.8	143.3	127.4	100.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	63.1	89.5	91.1	88.5	81.5	66.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	259.0	293.4	224.3	157.3	129.0	107.5
B/Colorado/06/2017 (B Victoria lineage) - Day 29	402.0	538.2	464.8	346.0	243.9	211.5
A/Michigan/45/2015 X-275 (H1N1) - Day 29	250.4	264.0	216.4	161.4	129.0	105.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	116.0	188.5	143.8	112.2	92.1	82.1

11. Primary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	0.9	0.7	0.9	0.8
B/Colorado/06/2017 (B Victoria lineage) - Day 1	1.2	1.2	0.9	0.6
A/Michigan/45/2015 X-275 (H1N1) - Day 1	0.9	0.8	0.9	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	1.4	1.4	0.9	0.8
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	1.1	0.9	0.8	0.7
B/Colorado/06/2017 (B Victoria lineage) - Day 29	1.3	1.2	0.7	0.6
A/Michigan/45/2015 X-275 (H1N1) - Day 29	1.1	0.9	0.8	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	1.6	1.2	0.8	0.7

12. Primary Outcome

Title	Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 29.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	36	39	40	37	41
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2)	27 65.9%	36 97.3%	36 90%	3 7.3%	0 0%	2 4.7%
B/Colorado/06/2017 (B Victoria lineage)	27 65.9%	25 67.6%	18 45%	0 0%	0 0%	5 11.6%
A/Michigan/45/2015 X-275 (H1N1)	27 65.9%	31 83.8%	36 90%	3 7.3%	0 0%	2 4.7%
B/Phuket/3073/2013 (B Yamagata lineage)	20 48.8%	22 59.5%	10 25%	3 7.3%	0 0%	2 4.7%

13. Primary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	36	39	40	37	41
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2)	2.1	2.5	2.6	1.0	1.0	1.0
B/Colorado/06/2017 (B Victoria lineage)	2.3	2.6	2.2	1.2	1.1	1.2
A/Michigan/45/2015 X-275 (H1N1)	2.1	2.5	2.4	1.0	1.0	1.1
B/Phuket/3073/2013 (B Yamagata lineage	1.8	2.1	1.6	1.2	1.2	1.2

14. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	106.8	147.7	101.9	151.6	121.2	118.5
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 1	108.9	113.4	94.0	199.4	81.9	101.0
A/Michigan/45/2015 X-275 (H1N1) - Day 1	3141.7	2697.5	2147.8	3703.3	2214.0	2764.2
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	479.4	577.8	630.3	860.1	447.8	539.2
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	379.1	671.9	456.5	848.9	741.9	567.0
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 29	302.2	305.1	248.4	463.3	304.8	291.6
A/Michigan/45/2015 X-275 (H1N1) - Day 29	5639.5	5435.2	4455.8	8539.5	9197.6	6021.9
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	1162.7	1437.4	1152.1	2053.5	1473.1	1291.7

15. Primary Outcome

Title	Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1 and Day 29 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	1.4	1.0	0.8	0.8
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 1	1.0	0.9	0.4	0.5
A/Michigan/45/2015 X-275 (H1N1) - Day 1	0.9	0.7	0.6	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	1.2	1.3	0.5	0.6
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	1.8	1.2	0.9	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 29	1.0	0.8	0.7	0.6
A/Michigan/45/2015 X-275 (H1N1) - Day 29	1.0	0.8	1.1	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	1.2	1.0	0.7	0.6

16. Primary Outcome

Title	Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	36	39	40	37	41
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2)	37 90.2%	42 113.5%	38 95%	60 146.3%	65 166.7%	56 130.2%
B/Maryland/15/2016 BX-69A (B Victoria lineage)	22 53.7%	19 51.4%	28 70%	20 48.8%	30 76.9%	34 79.1%
A/Michigan/45/2015 X-275 (H1N1)	15 36.6%	11 29.7%	21 52.5%	20 48.8%	41 105.1%	20 46.5%
B/Phuket/3073/2013 (B Yamagata lineage)	24 58.5%	14 37.8%	18 45%	18 43.9%	30 76.9%	22 51.2%

17. Primary Outcome

Title	Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab.
Time Frame	Day 1, Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 mL of 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 1	88 214.6%	95 256.8%	75 187.5%	90 219.5%	89 228.2%	90 209.3%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 1	78 190.2%	78 210.8%	68 170%	83 202.4%	71 182.1%	76 176.7%
A/Michigan/45/2015 X-275 (H1N1) - Day 1	100 243.9%	97 262.2%	98 245%	100 243.9%	97 248.7%	98 227.9%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 1	100 243.9%	97 262.2%	100 250%	95 231.7%	92 235.9%	100 232.6%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 29	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 29	95 231.7%	97 262.2%	95 237.5%	90 219.5%	92 235.9%	95 220.9%
A/Michigan/45/2015 X-275 (H1N1) - Day 29	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 29	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%

18. Primary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 29 titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	36	39	40	37	41
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2)	3.6	4.3	4.6	5.5	5.9	4.6
B/Maryland/15/2016 BX-69A (B Victoria lineage)	2.8	2.8	2.7	2.3	3.5	2.8
A/Michigan/45/2015 X-275 (H1N1)	1.8	1.9	2.2	2.1	4.2	2.1
B/Phuket/3073/2013 (B Yamagata lineage)	2.4	2.4	1.9	2.4	3.4	2.3

19. Secondary Outcome

Title	Number of Participants Reporting Protocol Specified Adverse Events of Special Interest (AESIs)
Description	Participants were queried at each visit for the occurrence of adverse events of special interest (AESIs) through approximately 12 months following the first study vaccination. AESIs include reports of tearing, dry mouth, and dry eyes.
Time Frame	Day 1 through Day 365

Outcome Measure Data

Analysis Population Description

The Safety Analysis population includes all participants who received study vaccination. Analyses for the safety population are based on vaccine actually received. One participant randomized to Flublok + AF03 group received Flublok due to a pharmacy error and is analyzed in the Flublok group.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	42	37	43
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

20. Secondary Outcome

Title	Number of Participants Reporting Medically-Attended Adverse Events (MAAEs), New-Onset Chronic Medical Conditions (NOCMCs), and Potentially Immune-Mediated Medical Conditions (PIMMCs)
Description	Participants were queried at each visit for the occurrence of medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs) through approximately 12 months following the first study vaccination.
Time Frame	Day 1 through Day 365

Outcome Measure Data

Analysis Population Description

The Safety Analysis population includes all participants who received the first study vaccination. Analyses for the safety population are based on vaccine actually received. One participant randomized to Flublok + AF03 group received Flublok due to a pharmacy error and is analyzed in the Flublok group.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	42	37	43
MAAEs	9 22%	13 35.1%	7 17.5%	8 19.5%	7 17.9%	10 23.3%
NOCMCs	1 2.4%	0 0%	0 0%	1 2.4%	1 2.6%	0 0%
PIMMCs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

21. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	325.5	326.2	234.7	456.6	408.2	355.1
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	387.9	367.6	269.1	627.1	509.8	491.0
A/Kansas/14/2017 (H3N2) - Day 90	33.8	67.9	38.2	69.4	50.1	62.2
A/Kansas/14/2017 (H3N2) - Day 118	203.5	213.6	274.6	369.1	254.9	212.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	797.3	1129.4	849.1	1502.0	1041.6	995.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	665.1	874.3	792.8	1228.9	905.1	1065.4
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	312.0	339.0	245.6	410.4	323.0	303.8
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	323.1	281.8	255.7	404.5	320.0	329.9

22. Secondary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	1.0	0.7	0.9	0.8
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	0.9	0.7	0.8	0.8
A/Kansas/14/2017 (H3N2) - Day 90	2.0	1.1	0.7	0.9
A/Kansas/14/2017 (H3N2) - Day 118	1.0	1.3	0.7	0.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.4	1.1	0.7	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1.3	1.2	0.7	0.9
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	1.1	0.8	0.8	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	0.9	0.8	0.8	0.8

23. Secondary Outcome

Title	Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-second vaccination titer < 1:10 and a post- second vaccination titer >= 1:40 or a pre-second vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	36	30	34	34	32	34
A/Brisbane/02/2018 IVR-190 (H1N1)	0 0%	0 0%	0 0%	6 14.6%	0 0%	6 14%
A/Kansas/14/2017 (H3N2)	67 163.4%	43 116.2%	74 185%	56 136.6%	53 135.9%	53 123.3%
B/Phuket/3073/2013 (B Yamagata lineage)	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
B/Maryland/15/2016 BX-69A (B Victoria lineage)	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

24. Secondary Outcome

Title	Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	100 243.9%	100 270.3%	92 230%	95 231.7%	95 243.6%	95 220.9%
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	100 243.9%	100 270.3%	91 227.5%	97 236.6%	97 248.7%	97 225.6%
A/Kansas/14/2017 (H3N2) - Day 90	41 100%	67 181.1%	50 125%	77 187.8%	59 151.3%	73 169.8%
A/Kansas/14/2017 (H3N2) - Day 118	92 224.4%	93 251.4%	94 235%	100 243.9%	91 233.3%	94 218.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	98 239%	100 270.3%	97 242.5%	97 236.6%	97 248.7%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	100 243.9%	100 270.3%	97 242.5%	100 243.9%	94 241%	100 232.6%

25. Secondary Outcome

Title	Geometric Mean Fold Rise in Hemagglutination Inhibition (HAI) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises at Day 118 were calculated as the Day 118 titer divided by the Day 90 titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Brisbane/02/2018 IVR-190 (H1N1)	1.1	1.1	1.2	1.3	1.3	1.4
A/Kansas/14/2017 (H3N2)	7.1	3.3	6.9	5.4	5.5	3.6
B/Phuket/3073/2013 (B Yamagata lineage)	0.8	0.8	1.0	0.8	0.9	1.1
B/Maryland/15/2016 BX-69A (B Victoria lineage)	1.1	0.9	1.0	1.0	1.0	1.1

26. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	90.1	91.5	72.4
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	107.8	111.8	79.2
A/Kansas/14/2017 (H3N2) - Day 90	35.8	49.0	36.5
A/Kansas/14/2017 (H3N2) - Day 118	48.5	51.0	45.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	104.0	156.9	137.0
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	115.3	158.2	150.5
B/Colorado/06/2017 (B Victoria lineage) - Day 90	286.7	391.7	294.8
B/Colorado/06/2017 (B Victoria lineage) - Day 118	373.3	474.0	400.4

27. Secondary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. The unadjuvanted Fluzone study arm is considered a reference group for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	37	40
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	1.0	0.8
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	1.0	0.7
A/Kansas/14/2017 (H3N2) - Day 90	1.4	1.0
A/Kansas/14/2017 (H3N2) - Day 118	1.1	0.9
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.5	1.3
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1.4	1.3
B/Colorado/06/2017 (B Victoria lineage) - Day 90	1.4	1.0
B/Colorado/06/2017 (B Victoria lineage) - Day 118	1.3	1.1

28. Secondary Outcome

Title	Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 90 through Day 118.
Time Frame	Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	36	30	34
A/Brisbane/02/2018 IVR-190 (H1N1)	6 14.6%	0 0%	0 0%
A/Kansas/14/2017 (H3N2)	8 19.5%	0 0%	0 0%
B/Phuket/3073/2013 (B Yamagata lineage)	3 7.3%	0 0%	0 0%
B/Colorado/06/2017 (B Victoria lineage)	8 19.5%	0 0%	0 0%

29. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises at Day 118 were calculated as the Day 118 titer divided by the Day 90 titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	36	30	34
A/Brisbane/02/2018 IVR-190 (H1N1)	1.3	1.2	1.2
A/Kansas/14/2017 (H3N2)	1.4	1.1	1.3
B/Phuket/3073/2013 (B Yamagata lineage)	1.2	1.0	1.1
B/Colorado/06/2017 (B Victoria lineage)	1.3	1.3	1.3

30. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	3375.3	3727.3	2488.0	4850.2	5622.8	3899.5
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	3891.7	3613.3	2895.1	6618.8	5654.7	4983.6
A/Kansas/14/2017 (H3N2) - Day 90	50.7	81.4	57.2	90.7	72.3	79.1
A/Kansas/14/2017 (H3N2) - Day 118	238.1	198.0	225.6	396.6	266.5	251.9
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	681.0	909.3	766.9	1371.5	953.5	754.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1087.2	1031.7	1086.9	1920.9	1234.9	1284.8
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	255.4	235.4	178.3	362.6	234.1	232.4
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	202.2	180.7	151.5	312.0	212.1	211.7

31. Secondary Outcome

Title	Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 90 and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 90 through Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 90	1.1	0.7	1.2	0.8
A/Brisbane/02/2018 IVR-190 (H1N1) - Day 118	0.9	0.7	0.9	0.8
A/Kansas/14/2017 (H3N2) - Day 90	1.6	1.1	0.8	0.9
A/Kansas/14/2017 (H3N2) - Day 118	0.8	0.9	0.7	0.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.3	1.1	0.7	0.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	0.9	1.0	0.6	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	0.9	0.7	0.6	0.6
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	0.9	0.7	0.7	0.7

32. Secondary Outcome

Title	Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-second vaccination titer < 1:10 and a post-second vaccination titer >= 1:40 or a pre-second vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	36	30	34	34	32	34
A/Brisbane/02/2018 IVR-190 (H1N1)	0 0%	0 0%	0 0%	9 22%	6 15.4%	3 7%
A/Kansas/14/2017 (H3N2)	58 141.5%	30 81.1%	44 110%	56 136.6%	38 97.4%	26 60.5%
B/Phuket/3073/2013 (B Yamagata lineage)	8 19.5%	3 8.1%	3 7.5%	0 0%	9 23.1%	12 27.9%
B/Maryland/15/2016 BX-69A (B Victoria lineage)	3 7.3%	0 0%	0 0%	0 0%	0 0%	0 0%

33. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2019/2020 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2019/2020 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises at Day 118 were calculated as the Day 118 titer divided by the Day 90 titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	36	30	34	34	32	34
A/Brisbane/02/2018 IVR-190 (H1N1)	1.0	1.0	1.3	1.4	1.1	1.3
A/Kansas/14/2017 (H3N2)	5.1	2.5	3.9	4.5	3.9	3.1
B/Phuket/3073/2013 (B Yamagata lineage)	1.7	1.2	1.5	1.5	1.3	1.7
B/Maryland/15/2016 BX-69A (B Victoria lineage)	0.8	0.9	0.9	0.9	0.9	0.9

34. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	296.6	582.8	343.0	398.7	469.4	347.5
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	248.9	520.8	266.6	602.3	506.4	408.9
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	224.4	456.9	245.6	565.1	444.1	383.9
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	320.0	570.2	404.5	962.2	839.0	554.9
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	441.2	525.7	400.9	480.1	402.0	344.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	322.8	338.5	254.8	422.2	311.1	286.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	312.0	339.0	245.6	410.4	323.0	303.8
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	323.1	281.8	255.7	404.5	320.0	329.9
A/Michigan/45/2015 X-275 (H1N1) - Day 8	603.2	561.3	472.6	673.3	701.1	542.6
A/Michigan/45/2015 X-275 (H1N1) - Day 57	629.0	582.8	440.3	897.3	771.9	645.4
A/Michigan/45/2015 X-275 (H1N1) - Day 90	526.9	548.6	366.9	757.7	689.8	571.8
A/Michigan/45/2015 X-275 (H1N1) - Day 118	586.9	519.8	361.6	868.9	697.9	715.9
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	714.3	1061.3	889.5	1045.0	1019.0	875.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	629.0	905.1	740.6	1133.8	839.8	817.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	797.3	1129.4	849.1	1502.0	1041.6	995.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	665.1	874.3	792.8	1228.9	905.1	1065.4

35. Secondary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	2.0	1.2	1.2	0.9
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	2.1	1.1	0.8	0.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	2.0	1.1	0.8	0.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	1.8	1.3	0.9	0.6
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	1.2	0.9	0.8	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	1.0	0.8	0.7	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	1.1	0.8	0.8	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	0.9	0.8	0.8	0.8
A/Michigan/45/2015 X-275 (H1N1) - Day 8	0.9	0.8	1.0	0.8
A/Michigan/45/2015 X-275 (H1N1) - Day 57	0.9	0.7	0.9	0.7
A/Michigan/45/2015 X-275 (H1N1) - Day 90	1.0	0.7	0.9	0.8
A/Michigan/45/2015 X-275 (H1N1) - Day 118	0.9	0.6	0.8	0.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	1.5	1.2	1.0	0.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	1.4	1.2	0.7	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.4	1.1	0.7	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1.3	1.2	0.7	0.9

36. Secondary Outcome

Title	Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	27 65.9%	35 94.6%	30 75%	29 70.7%	47 120.5%	43 100%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	25 61%	30 81.1%	32 80%	43 104.9%	54 138.5%	44 102.3%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	24 58.5%	25 67.6%	32 80%	41 100%	41 105.1%	43 100%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	42 102.4%	37 100%	50 125%	71 173.2%	72 184.6%	56 130.2%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	27 65.9%	35 94.6%	35 87.5%	22 53.7%	47 120.5%	26 60.5%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	20 48.8%	22 59.5%	24 60%	15 36.6%	35 89.7%	22 51.2%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	22 53.7%	22 59.5%	24 60%	15 36.6%	35 89.7%	23 53.5%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	22 53.7%	17 45.9%	26 65%	15 36.6%	31 79.5%	29 67.4%
A/Michigan/45/2015 X-275 (H1N1) - Day 8	22 53.7%	19 51.4%	23 57.5%	24 58.5%	39 100%	24 55.8%
A/Michigan/45/2015 X-275 (H1N1) - Day 57	23 56.1%	24 64.9%	24 60%	33 80.5%	46 117.9%	24 55.8%
A/Michigan/45/2015 X-275 (H1N1) - Day 90	20 48.8%	17 45.9%	16 40%	28 68.3%	38 97.4%	23 53.5%
A/Michigan/45/2015 X-275 (H1N1) - Day 118	22 53.7%	10 27%	24 60%	32 78%	47 120.5%	44 102.3%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	20 48.8%	16 43.2%	20 50%	12 29.3%	29 74.4%	21 48.8%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	15 36.6%	19 51.4%	16 40%	18 43.9%	30 76.9%	22 51.2%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	22 53.7%	14 37.8%	13 32.5%	26 63.4%	27 69.2%	30 69.8%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	17 41.5%	13 35.1%	15 37.5%	15 36.6%	16 41%	35 81.4%

37. Secondary Outcome

Title	Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	100 243.9%	100 270.3%	100 250%	100 243.9%	97 248.7%	100 232.6%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	100 243.9%	100 270.3%	97 242.5%	100 243.9%	100 256.4%	100 232.6%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	98 239%	100 270.3%	97 242.5%	100 243.9%	100 256.4%	98 227.9%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	100 243.9%	100 270.3%	97 242.5%	100 243.9%	100 256.4%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	100 243.9%	100 270.3%	100 250%	100 243.9%	97 248.7%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	100 243.9%	100 270.3%	97 242.5%	100 243.9%	97 248.7%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	98 239%	100 270.3%	97 242.5%	97 236.6%	97 248.7%	100 232.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	100 243.9%	100 270.3%	97 242.5%	100 243.9%	94 241%	100 232.6%
A/Michigan/45/2015 X-275 (H1N1) - Day 8	100 243.9%	100 270.3%	98 245%	100 243.9%	97 248.7%	98 227.9%
A/Michigan/45/2015 X-275 (H1N1) - Day 57	100 243.9%	100 270.3%	95 237.5%	100 243.9%	97 248.7%	98 227.9%
A/Michigan/45/2015 X-275 (H1N1) - Day 90	100 243.9%	100 270.3%	95 237.5%	100 243.9%	97 248.7%	98 227.9%
A/Michigan/45/2015 X-275 (H1N1) - Day 118	100 243.9%	100 270.3%	94 235%	100 243.9%	97 248.7%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%

38. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for HAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	2.6	3.0	3.5	2.4	3.6	3.2
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	2.2	2.7	3.0	3.6	3.8	3.6
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	2.0	2.2	2.8	3.4	3.3	3.3
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	3.1	2.8	5.0	6.1	6.7	5.3
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	3.1	3.5	3.3	1.9	3.8	2.6
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	2.2	2.3	2.2	1.7	2.8	2.1
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	2.2	2.4	2.1	1.7	2.9	2.3
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	2.3	2.1	2.3	1.6	2.9	2.6
A/Michigan/45/2015 X-275 (H1N1) - Day 8	2.5	2.9	2.7	2.3	3.8	2.3
A/Michigan/45/2015 X-275 (H1N1) - Day 57	2.4	3.0	2.7	2.8	4.2	2.6
A/Michigan/45/2015 X-275 (H1N1) - Day 90	2.2	2.7	2.3	2.4	3.8	2.4
A/Michigan/45/2015 X-275 (H1N1) - Day 118	2.2	2.2	2.5	2.7	3.8	3.0
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	1.9	2.2	1.8	1.7	3.1	2.2
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	1.7	1.9	1.5	1.8	2.5	2.1
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	2.2	2.2	1.8	2.5	3.1	2.5
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1.8	1.8	1.8	2.0	2.6	2.8

39. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	441.2	501.7	394.0
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	262.2	260.4	202.8
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	201.0	201.6	148.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	258.9	242.5	200.2
B/Colorado/06/2017 (B Victoria lineage) - Day 8	385.4	566.6	415.0
B/Colorado/06/2017 (B Victoria lineage) - Day 57	309.1	427.8	311.4
B/Colorado/06/2017 (B Victoria lineage) - Day 90	286.7	391.7	294.8
B/Colorado/06/2017 (B Victoria lineage) - Day 118	373.3	474.0	400.4
A/Michigan/45/2015 X-275 (H1N1) - Day 8	398.7	419.9	352.0
A/Michigan/45/2015 X-275 (H1N1) - Day 57	218.6	220.0	155.7
A/Michigan/45/2015 X-275 (H1N1) - Day 90	189.5	176.2	125.1
A/Michigan/45/2015 X-275 (H1N1) - Day 118	261.4	218.6	177.2
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	137.4	208.0	174.5
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	117.1	177.4	157.1
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	104.0	156.9	137.0
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	115.3	158.2	150.5

40. Secondary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. The unadjuvanted Fluzone study arm is considered a reference group for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	37	40
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	1.1	0.9
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	1.0	0.8
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	1.0	0.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	0.9	0.8
B/Colorado/06/2017 (B Victoria lineage) - Day 8	1.5	1.1
B/Colorado/06/2017 (B Victoria lineage) - Day 57	1.4	1.0
B/Colorado/06/2017 (B Victoria lineage) - Day 90	1.4	1.0
B/Colorado/06/2017 (B Victoria lineage) - Day 118	1.3	1.1
A/Michigan/45/2015 X-275 (H1N1) - Day 8	1.1	0.9
A/Michigan/45/2015 X-275 (H1N1) - Day 57	1.0	0.7
A/Michigan/45/2015 X-275 (H1N1) - Day 90	0.9	0.7
A/Michigan/45/2015 X-275 (H1N1) - Day 118	0.8	0.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	1.5	1.3
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	1.5	1.3
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.5	1.3
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1.4	1.3

41. Secondary Outcome

Title	Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 8, 57, 90, and 118.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	49 119.5%	62 167.6%	50 125%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	20 48.8%	22 59.5%	24 60%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	12 29.3%	8 21.6%	13 32.5%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	28 68.3%	23 62.2%	32 80%
B/Colorado/06/2017 (B Victoria lineage) - Day 8	20 48.8%	30 81.1%	13 32.5%
B/Colorado/06/2017 (B Victoria lineage) - Day 57	18 43.9%	16 43.2%	8 20%
B/Colorado/06/2017 (B Victoria lineage) - Day 90	10 24.4%	8 21.6%	5 12.5%
B/Colorado/06/2017 (B Victoria lineage) - Day 118	19 46.3%	20 54.1%	9 22.5%
A/Michigan/45/2015 X-275 (H1N1) - Day 8	46 112.2%	57 154.1%	50 125%
A/Michigan/45/2015 X-275 (H1N1) - Day 57	15 36.6%	22 59.5%	11 27.5%
A/Michigan/45/2015 X-275 (H1N1) - Day 90	10 24.4%	11 29.7%	3 7.5%
A/Michigan/45/2015 X-275 (H1N1) - Day 118	25 61%	13 35.1%	24 60%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	27 65.9%	30 81.1%	20 50%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	18 43.9%	16 43.2%	8 20%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	12 29.3%	11 29.7%	5 12.5%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	17 41.5%	10 27%	6 15%

42. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	3.6	4.3	4.3
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	2.0	2.2	2.4
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	1.6	1.7	1.8
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	2.2	2.1	2.7
B/Colorado/06/2017 (B Victoria lineage) - Day 8	2.2	2.7	1.9
B/Colorado/06/2017 (B Victoria lineage) - Day 57	1.8	2.0	1.5
B/Colorado/06/2017 (B Victoria lineage) - Day 90	1.6	1.9	1.5
B/Colorado/06/2017 (B Victoria lineage) - Day 118	2.2	2.5	2.0
A/Michigan/45/2015 X-275 (H1N1) - Day 8	3.4	3.9	3.6
A/Michigan/45/2015 X-275 (H1N1) - Day 57	1.8	2.0	1.8
A/Michigan/45/2015 X-275 (H1N1) - Day 90	1.6	1.6	1.4
A/Michigan/45/2015 X-275 (H1N1) - Day 118	2.4	2.0	2.2
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	2.2	2.3	1.9
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	1.8	2.0	1.7
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.6	1.7	1.5
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1.9	1.7	1.7

43. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	140.6	271.9	154.0	168.8	210.6	148.5
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	150.2	312.9	195.6	354.4	309.0	259.3
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	132.1	244.2	152.8	273.4	265.7	202.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	161.8	257.6	224.1	446.6	409.5	276.8
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	309.6	333.9	261.6	369.0	243.2	255.4
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	365.7	358.1	232.1	439.5	300.2	306.0
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	255.4	235.4	178.3	362.6	234.1	232.4
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	202.2	180.7	151.5	312.0	212.1	211.7
A/Michigan/45/2015 X-275 (H1N1) - Day 8	6824.7	7795.4	5604.4	6666.4	8444.6	5925.2
A/Michigan/45/2015 X-275 (H1N1) - Day 57	3437.4	4437.2	3335.0	8293.9	6502.7	5791.6
A/Michigan/45/2015 X-275 (H1N1) - Day 90	4623.9	4965.3	3255.1	6518.8	6113.7	4837.8
A/Michigan/45/2015 X-275 (H1N1) - Day 118	5094.4	5393.5	3153.9	8037.0	6631.4	6168.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	1126.1	1049.1	1095.1	1515.8	1154.5	824.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	859.6	1225.3	1037.6	1959.7	1243.1	1173.0
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	681.0	909.3	766.9	1371.5	953.5	754.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	1087.2	1031.7	1086.9	1920.9	1234.9	1284.8

44. Secondary Outcome

Title	Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 8, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	1.9	1.1	1.2	0.9
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	2.1	1.3	0.9	0.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	1.8	1.2	1.0	0.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	1.6	1.4	0.9	0.6
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	1.1	0.8	0.7	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	1.0	0.6	0.7	0.7
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	0.9	0.7	0.6	0.6
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	0.9	0.7	0.7	0.7
A/Michigan/45/2015 X-275 (H1N1) - Day 8	1.1	0.8	1.3	0.9
A/Michigan/45/2015 X-275 (H1N1) - Day 57	1.3	1.0	0.8	0.7
A/Michigan/45/2015 X-275 (H1N1) - Day 90	1.1	0.7	0.9	0.7
A/Michigan/45/2015 X-275 (H1N1) - Day 118	1.1	0.6	0.8	0.8
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	0.9	1.0	0.8	0.5
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	1.4	1.2	0.6	0.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.3	1.1	0.7	0.6
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	0.9	1.0	0.6	0.7

45. Secondary Outcome

Title	Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	10 24.4%	16 43.2%	20 50%	15 36.6%	11 28.2%	7 16.3%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	10 24.4%	22 59.5%	18 45%	38 92.7%	27 69.2%	24 55.8%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	12 29.3%	11 29.7%	13 32.5%	23 56.1%	22 56.4%	10 23.3%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	14 34.1%	10 27%	24 60%	32 78%	38 97.4%	24 55.8%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	15 36.6%	24 64.9%	30 75%	15 36.6%	34 87.2%	31 72.1%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	25 61%	27 73%	32 80%	25 61%	35 89.7%	34 79.1%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	17 41.5%	19 51.4%	18 45%	13 31.7%	30 76.9%	25 58.1%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	14 34.1%	17 45.9%	18 45%	9 22%	28 71.8%	26 60.5%
A/Michigan/45/2015 X-275 (H1N1) - Day 8	17 41.5%	24 64.9%	20 50%	20 48.8%	37 94.9%	24 55.8%
A/Michigan/45/2015 X-275 (H1N1) - Day 57	13 31.7%	11 29.7%	8 20%	23 56.1%	27 69.2%	17 39.5%
A/Michigan/45/2015 X-275 (H1N1) - Day 90	12 29.3%	11 29.7%	11 27.5%	8 19.5%	30 76.9%	13 30.2%
A/Michigan/45/2015 X-275 (H1N1) - Day 118	11 26.8%	10 27%	18 45%	18 43.9%	31 79.5%	21 48.8%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	32 78%	11 29.7%	23 57.5%	24 58.5%	24 61.5%	19 44.2%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	28 68.3%	16 43.2%	21 52.5%	18 43.9%	22 56.4%	27 62.8%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	15 36.6%	11 29.7%	8 20%	15 36.6%	22 56.4%	15 34.9%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	22 53.7%	13 35.1%	18 45%	18 43.9%	16 41%	21 48.8%

46. Secondary Outcome

Title	Percentage of Participants With Neutralizing (Neut) Titer of 1:40 or Greater Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which is a geometric mean titer of the replicates was reported by the lab.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	95 231.7%	100 270.3%	95 237.5%	95 231.7%	95 243.6%	93 216.3%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	98 239%	100 270.3%	97 242.5%	100 243.9%	100 256.4%	100 232.6%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	95 231.7%	100 270.3%	89 222.5%	97 236.6%	95 243.6%	93 216.3%
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	94 229.3%	100 270.3%	97 242.5%	100 243.9%	97 248.7%	97 225.6%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	93 226.8%	97 262.2%	90 225%	95 231.7%	87 223.1%	98 227.9%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	95 231.7%	100 270.3%	95 237.5%	90 219.5%	89 228.2%	98 227.9%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	95 231.7%	100 270.3%	82 205%	87 212.2%	89 228.2%	93 216.3%
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	89 217.1%	90 243.2%	71 177.5%	85 207.3%	91 233.3%	94 218.6%
A/Michigan/45/2015 X-275 (H1N1) - Day 8	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
A/Michigan/45/2015 X-275 (H1N1) - Day 57	98 239%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
A/Michigan/45/2015 X-275 (H1N1) - Day 90	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
A/Michigan/45/2015 X-275 (H1N1) - Day 118	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	98 239%	97 262.2%	100 250%	100 243.9%	97 248.7%	95 220.9%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	100 243.9%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	100 243.9%	100 270.3%	100 250%	100 243.9%	97 248.7%	100 232.6%

47. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against the 2018/2019 Quadrivalent Influenza Vaccine (QIV) Strains
Description	Blood was collected for Neut assay which was conducted with the 2018/2019 QIV viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 8 (or Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 8, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood sample for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 8	1.3	1.8	1.5	1.1	1.7	1.3
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 57	1.4	2.1	2.0	2.3	2.5	2.1
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 90	1.2	1.6	1.6	1.8	2.1	1.7
A/Singapore/INFIMH-16-0019/2016 IVR-186 (H3N2) - Day 118	1.7	1.7	2.4	3.0	3.5	2.4
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 8	2.8	2.9	2.8	1.9	3.0	2.5
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 57	3.2	3.2	2.5	2.2	3.6	2.9
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 90	2.3	2.1	2.0	1.8	2.8	2.3
B/Maryland/15/2016 BX-69A (B Victoria lineage) - Day 118	1.8	1.7	1.7	1.5	2.5	2.2
A/Michigan/45/2015 X-275 (H1N1) - Day 8	2.2	2.9	2.6	1.8	3.8	2.1
A/Michigan/45/2015 X-275 (H1N1) - Day 57	1.0	1.6	1.7	2.1	3.0	2.0
A/Michigan/45/2015 X-275 (H1N1) - Day 90	1.5	1.7	1.6	1.6	2.9	1.7
A/Michigan/45/2015 X-275 (H1N1) - Day 118	1.5	1.7	1.8	2.0	3.0	2.3
B/Phuket/3073/2013 (B Yamagata lineage) - Day 8	2.3	1.8	1.7	1.8	2.6	1.5
B/Phuket/3073/2013 (B Yamagata lineage) - Day 57	1.8	2.1	1.6	2.2	2.7	2.1
B/Phuket/3073/2013 (B Yamagata lineage) - Day 90	1.4	1.5	1.2	1.6	2.1	1.4
B/Phuket/3073/2013 (B Yamagata lineage) - Day 118	2.2	1.7	1.9	2.3	2.4	2.6

48. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 post first study vaccination.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 1	59.5	113.1	70.3	87.8	78.6	63.5
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	189.5	440.0	296.0	261.2	357.0	299.6
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	184.7	415.0	282.6	400.9	440.0	366.3
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	116.1	272.9	167.5	314.5	317.0	281.9
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	112.2	264.0	155.7	272.7	288.7	244.6
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	215.6	351.0	291.9	583.9	580.6	388.4
A/Aksaray/4048/2016 [H3N2] - Day 1	72.9	141.7	76.6	112.2	80.0	87.6
A/Aksaray/4048/2016 [H3N2] - Day 8	178.6	452.5	259.9	314.6	394.7	339.0
A/Aksaray/4048/2016 [H3N2] - Day 29	174.1	415.0	222.3	433.4	456.8	402.0
A/Aksaray/4048/2016 [H3N2] - Day 57	146.7	338.5	188.5	407.9	423.8	366.3
A/Aksaray/4048/2016 [H3N2] - Day 90	140.9	299.1	157.1	331.6	323.0	293.4
A/Aksaray/4048/2016 [H3N2] - Day 118	320.0	496.4	438.9	877.8	812.2	578.0
A/Kenya/105/2017 [H3N2] - Day 1	63.7	123.1	67.3	105.7	69.8	78.0
A/Kenya/105/2017 [H3N2] - Day 8	184.7	483.2	251.1	312.0	405.6	374.3
A/Kenya/105/2017 [H3N2] - Day 29	265.7	646.2	311.6	656.9	709.5	650.9
A/Kenya/105/2017 [H3N2] - Day 57	182.2	435.9	216.2	452.5	416.0	405.5
A/Kenya/105/2017 [H3N2] - Day 90	202.7	508.0	226.3	545.4	516.0	460.5
A/Kenya/105/2017 [H3N2] - Day 118	269.1	417.4	301.0	784.7	661.1	543.7
A/Louisiana/13/2017 [H3N2] - Day 1	29.8	61.5	29.8	43.5	33.0	34.8
A/Louisiana/13/2017 [H3N2] - Day 8	103.1	248.5	121.3	130.6	148.7	117.9
A/Louisiana/13/2017 [H3N2] - Day 29	113.1	271.7	129.3	226.3	196.6	180.1
A/Louisiana/13/2017 [H3N2] - Day 57	74.6	169.2	86.8	177.5	132.7	127.4
A/Louisiana/13/2017 [H3N2] - Day 90	72.3	163.1	77.1	176.4	129.0	124.5
A/Louisiana/13/2017 [H3N2] - Day 118	256.4	278.6	253.1	673.5	521.0	365.3
A/Michigan/84/2016 [H3N2] - Day 1	82.1	98.3	62.8	98.0	58.1	74.9
A/Michigan/84/2016 [H3N2] - Day 8	115.1	169.2	96.8	129.5	100.5	106.8
A/Michigan/84/2016 [H3N2] - Day 29	124.2	152.5	94.7	168.5	108.0	121.1
A/Michigan/84/2016 [H3N2] - Day 57	95.1	131.4	75.7	154.5	81.5	106.6
A/Michigan/84/2016 [H3N2] - Day 90	99.7	137.2	79.3	162.9	78.5	111.2
A/Michigan/84/2016 [H3N2] - Day 118	129.5	183.8	121.5	323.3	153.2	180.8

49. Secondary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Against Heterologous H1 and H3 Influenza Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms was calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 1	1.9	1.2	0.9	0.7
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	2.3	1.6	1.4	1.1
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	2.2	1.5	1.1	0.9
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	2.4	1.4	1.0	0.9
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	2.4	1.4	1.1	0.9
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	1.6	1.4	1.0	0.7
A/Aksaray/4048/2016 [H3N2] - Day 1	1.9	1.1	0.7	0.8
A/Aksaray/4048/2016 [H3N2] - Day 8	2.5	1.5	1.3	1.1
A/Aksaray/4048/2016 [H3N2] - Day 29	2.4	1.3	1.1	0.9
A/Aksaray/4048/2016 [H3N2] - Day 57	2.3	1.3	1.0	0.9
A/Aksaray/4048/2016 [H3N2] - Day 90	2.1	1.1	1.0	0.9
A/Aksaray/4048/2016 [H3N2] - Day 118	1.6	1.4	0.9	0.7
A/Kenya/105/2017 [H3N2] - Day 1	1.9	1.1	0.7	0.7
A/Kenya/105/2017 [H3N2] - Day 8	2.6	1.4	1.3	1.2
A/Kenya/105/2017 [H3N2] - Day 29	2.4	1.2	1.1	1.0
A/Kenya/105/2017 [H3N2] - Day 57	2.4	1.2	0.9	0.9
A/Kenya/105/2017 [H3N2] - Day 90	2.5	1.1	0.9	0.8
A/Kenya/105/2017 [H3N2] - Day 118	1.6	1.1	0.8	0.7
A/Louisiana/13/2017 [H3N2] - Day 1	2.1	1.0	0.8	0.8
A/Louisiana/13/2017 [H3N2] - Day 8	2.4	1.2	1.1	0.9
A/Louisiana/13/2017 [H3N2] - Day 29	2.4	1.1	0.9	0.8
A/Louisiana/13/2017 [H3N2] - Day 57	2.3	1.2	0.7	0.7
A/Louisiana/13/2017 [H3N2] - Day 90	2.3	1.1	0.7	0.7
A/Louisiana/13/2017 [H3N2] - Day 118	1.1	1.0	0.8	0.5
A/Michigan/84/2016 [H3N2] - Day 1	1.2	0.8	0.6	0.8
A/Michigan/84/2016 [H3N2] - Day 8	1.5	0.8	0.8	0.8
A/Michigan/84/2016 [H3N2] - Day 29	1.2	0.8	0.6	0.7
A/Michigan/84/2016 [H3N2] - Day 57	1.4	0.8	0.5	0.7
A/Michigan/84/2016 [H3N2] - Day 90	1.4	0.8	0.5	0.7
A/Michigan/84/2016 [H3N2] - Day 118	1.4	0.9	0.5	0.6

50. Secondary Outcome

Title	Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Titer Seroconversion Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. HAI seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	44 107.3%	38 102.7%	33 82.5%	27 65.9%	50 128.2%	48 111.6%
A/Aksaray/4048/2016 [H3N2] - Day 8	27 65.9%	30 81.1%	30 75%	29 70.7%	47 120.5%	40 93%
A/Kenya/105/2017 [H3N2] - Day 8	32 78%	38 102.7%	35 87.5%	32 78%	58 148.7%	57 132.6%
A/Louisiana/13/2017 [H3N2] - Day 8	39 95.1%	41 110.8%	45 112.5%	29 70.7%	47 120.5%	40 93%
A/Michigan/84/2016 [H3N2] - Day 8	10 24.4%	11 29.7%	10 25%	5 12.2%	11 28.2%	7 16.3%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	37 90.2%	31 83.8%	36 90%	55 134.1%	57 146.2%	63 146.5%
A/Aksaray/4048/2016 [H3N2] - Day 29	27 65.9%	31 83.8%	31 77.5%	48 117.1%	57 146.2%	59 137.2%
A/Kenya/105/2017 [H3N2] - Day 29	51 124.4%	56 151.4%	51 127.5%	65 158.5%	78 200%	78 181.4%
A/Louisiana/13/2017 [H3N2] - Day 29	41 100%	53 143.2%	56 140%	53 129.3%	73 187.2%	59 137.2%
A/Michigan/84/2016 [H3N2] - Day 29	5 12.2%	8 21.6%	8 20%	10 24.4%	16 41%	12 27.9%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	18 43.9%	24 64.9%	26 65%	40 97.6%	49 125.6%	46 107%
A/Aksaray/4048/2016 [H3N2] - Day 57	23 56.1%	27 73%	29 72.5%	40 97.6%	57 146.2%	51 118.6%
A/Kenya/105/2017 [H3N2] - Day 57	23 56.1%	35 94.6%	39 97.5%	50 122%	62 159%	66 153.5%
A/Louisiana/13/2017 [H3N2] - Day 57	25 61%	30 81.1%	32 80%	45 109.8%	46 117.9%	44 102.3%
A/Michigan/84/2016 [H3N2] - Day 57	3 7.3%	8 21.6%	5 12.5%	8 19.5%	11 28.2%	10 23.3%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	20 48.8%	19 51.4%	24 60%	38 92.7%	38 97.4%	45 104.7%
A/Aksaray/4048/2016 [H3N2] - Day 90	20 48.8%	19 51.4%	24 60%	38 92.7%	41 105.1%	45 104.7%
A/Kenya/105/2017 [H3N2] - Day 90	34 82.9%	36 97.3%	39 97.5%	59 143.9%	62 159%	65 151.2%
A/Louisiana/13/2017 [H3N2] - Day 90	27 65.9%	22 59.5%	24 60%	46 112.2%	43 110.3%	48 111.6%
A/Michigan/84/2016 [H3N2] - Day 90	2 4.9%	6 16.2%	5 12.5%	8 19.5%	14 35.9%	13 30.2%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	53 129.3%	33 89.2%	47 117.5%	71 173.2%	69 176.9%	79 183.7%
A/Aksaray/4048/2016 [H3N2] - Day 118	58 141.5%	37 100%	62 155%	79 192.7%	75 192.3%	76 176.7%
A/Kenya/105/2017 [H3N2] - Day 118	56 136.6%	30 81.1%	62 155%	74 180.5%	88 225.6%	82 190.7%
A/Louisiana/13/2017 [H3N2] - Day 118	78 190.2%	47 127%	82 205%	85 207.3%	91 233.3%	91 211.6%
A/Michigan/84/2016 [H3N2] - Day 118	11 26.8%	13 35.1%	15 37.5%	38 92.7%	38 97.4%	26 60.5%

51. Secondary Outcome

Title	Percentage of Participants With Hemagglutination Inhibition (HAI) Titer of 1:40 or Greater Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 1	78 190.2%	78 210.8%	73 182.5%	71 173.2%	71 182.1%	69 160.5%
A/Aksaray/4048/2016 [H3N2] - Day 1	78 190.2%	81 218.9%	70 175%	80 195.1%	71 182.1%	81 188.4%
A/Kenya/105/2017 [H3N2] - Day 1	78 190.2%	86 232.4%	70 175%	90 219.5%	74 189.7%	86 200%
A/Louisiana/13/2017 [H3N2] - Day 1	54 131.7%	68 183.8%	43 107.5%	56 136.6%	47 120.5%	52 120.9%
A/Michigan/84/2016 [H3N2] - Day 1	78 190.2%	81 218.9%	68 170%	80 195.1%	66 169.2%	83 193%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	98 239%	100 270.3%	100 250%	93 226.8%	92 235.9%	100 232.6%
A/Aksaray/4048/2016 [H3N2] - Day 8	98 239%	100 270.3%	98 245%	100 243.9%	97 248.7%	100 232.6%
A/Kenya/105/2017 [H3N2] - Day 8	98 239%	100 270.3%	98 245%	100 243.9%	97 248.7%	100 232.6%
A/Louisiana/13/2017 [H3N2] - Day 8	88 214.6%	95 256.8%	88 220%	88 214.6%	89 228.2%	86 200%
A/Michigan/84/2016 [H3N2] - Day 8	93 226.8%	92 248.6%	93 232.5%	88 214.6%	79 202.6%	93 216.3%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	95 231.7%	100 270.3%	97 242.5%	98 239%	95 243.6%	98 227.9%
A/Aksaray/4048/2016 [H3N2] - Day 29	95 231.7%	100 270.3%	97 242.5%	100 243.9%	100 256.4%	100 232.6%
A/Kenya/105/2017 [H3N2] - Day 29	98 239%	100 270.3%	100 250%	100 243.9%	100 256.4%	100 232.6%
A/Louisiana/13/2017 [H3N2] - Day 29	90 219.5%	97 262.2%	95 237.5%	95 231.7%	97 248.7%	95 220.9%
A/Michigan/84/2016 [H3N2] - Day 29	98 239%	94 254.1%	87 217.5%	90 219.5%	78 200%	90 209.3%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	83 202.4%	100 270.3%	92 230%	95 231.7%	95 243.6%	95 220.9%
A/Aksaray/4048/2016 [H3N2] - Day 57	90 219.5%	100 270.3%	97 242.5%	100 243.9%	97 248.7%	100 232.6%
A/Kenya/105/2017 [H3N2] - Day 57	95 231.7%	100 270.3%	95 237.5%	100 243.9%	100 256.4%	100 232.6%
A/Louisiana/13/2017 [H3N2] - Day 57	78 190.2%	95 256.8%	82 205%	95 231.7%	92 235.9%	90 209.3%
A/Michigan/84/2016 [H3N2] - Day 57	83 202.4%	89 240.5%	82 205%	88 214.6%	76 194.9%	88 204.7%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	85 207.3%	100 270.3%	92 230%	97 236.6%	95 243.6%	95 220.9%
A/Aksaray/4048/2016 [H3N2] - Day 90	90 219.5%	100 270.3%	92 230%	100 243.9%	97 248.7%	100 232.6%
A/Kenya/105/2017 [H3N2] - Day 90	95 231.7%	100 270.3%	95 237.5%	100 243.9%	100 256.4%	100 232.6%
A/Louisiana/13/2017 [H3N2] - Day 90	78 190.2%	94 254.1%	74 185%	97 236.6%	89 228.2%	93 216.3%
A/Michigan/84/2016 [H3N2] - Day 90	83 202.4%	89 240.5%	79 197.5%	95 231.7%	76 194.9%	85 197.7%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	94 229.3%	100 270.3%	94 235%	100 243.9%	97 248.7%	100 232.6%
A/Aksaray/4048/2016 [H3N2] - Day 118	100 243.9%	100 270.3%	94 235%	100 243.9%	100 256.4%	100 232.6%
A/Kenya/105/2017 [H3N2] - Day 118	100 243.9%	100 270.3%	97 242.5%	100 243.9%	100 256.4%	100 232.6%
A/Louisiana/13/2017 [H3N2] - Day 118	97 236.6%	97 262.2%	94 235%	100 243.9%	97 248.7%	100 232.6%
A/Michigan/84/2016 [H3N2] - Day 118	94 229.3%	93 251.4%	88 220%	97 236.6%	84 215.4%	91 211.6%

52. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition (HAI) Titers Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for HAI assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 29, Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid HAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	3.2	3.9	4.2	3.0	4.5	4.7
A/Aksaray/4048/2016 [H3N2] - Day 8	2.4	3.2	3.4	2.8	4.9	3.9
A/Kenya/105/2017 [H3N2] - Day 8	2.9	3.9	3.7	3.0	5.8	4.8
A/Louisiana/13/2017 [H3N2] - Day 8	3.5	4.0	4.1	3.0	4.5	3.4
A/Michigan/84/2016 [H3N2] - Day 8	1.4	1.7	1.5	1.3	1.7	1.4
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	3.1	3.4	4.2	4.6	5.2	5.5
A/Aksaray/4048/2016 [H3N2] - Day 29	2.4	2.7	3.1	3.8	5.3	4.4
A/Kenya/105/2017 [H3N2] - Day 29	4.2	4.8	4.9	6.1	9.5	8.1
A/Louisiana/13/2017 [H3N2] - Day 29	3.8	4.2	4.6	5.0	5.7	5.1
A/Michigan/84/2016 [H3N2] - Day 29	1.5	1.6	1.5	1.7	1.8	1.6
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	2.0	2.4	2.6	3.6	3.9	4.2
A/Aksaray/4048/2016 [H3N2] - Day 57	2.0	2.4	2.7	3.6	5.1	4.0
A/Kenya/105/2017 [H3N2] - Day 57	2.9	3.5	3.6	4.2	5.8	5.0
A/Louisiana/13/2017 [H3N2] - Day 57	2.6	2.8	3.3	3.9	4.0	3.6
A/Michigan/84/2016 [H3N2] - Day 57	1.2	1.3	1.2	1.5	1.4	1.4
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	1.9	2.1	2.4	3.1	3.5	3.6
A/Aksaray/4048/2016 [H3N2] - Day 90	1.9	1.9	2.3	2.9	3.9	3.2
A/Kenya/105/2017 [H3N2] - Day 90	3.2	3.8	3.8	5.1	7.1	5.7
A/Louisiana/13/2017 [H3N2] - Day 90	2.4	2.5	2.9	3.8	3.9	3.5
A/Michigan/84/2016 [H3N2] - Day 90	1.2	1.4	1.3	1.6	1.4	1.5
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	4.1	2.8	4.9	6.8	8.1	6.6
A/Aksaray/4048/2016 [H3N2] - Day 118	5.1	3.1	6.5	8.1	11.0	6.9
A/Kenya/105/2017 [H3N2] - Day 118	4.8	3.1	5.2	7.8	10.4	7.5
A/Louisiana/13/2017 [H3N2] - Day 118	9.8	4.1	9.7	15.5	16.5	11.1
A/Michigan/84/2016 [H3N2] - Day 118	1.7	1.6	2.0	2.9	2.8	2.4

53. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Townsville/51/2016 H6N2 - Day 1	16.6	20.2	14.5
A/Townsville/51/2016 H6N2 - Day 8	34.1	49.6	35.1
A/Townsville/51/2016 H6N2 - Day 29	21.9	35.6	23.3
A/Townsville/51/2016 H6N2 - Day 57	26.2	37.1	24.2
A/Townsville/51/2016 H6N2 - Day 90	22.7	34.6	24.0
A/Townsville/51/2016 H6N2 - Day 118	32.4	39.1	29.5
A/Cameroon/9766/2017 H6N1 - Day 1	48.2	47.3	40.0
A/Cameroon/9766/2017 H6N1 - Day 8	104.0	117.5	91.1
A/Cameroon/9766/2017 H6N1 - Day 29	80.7	95.1	68.2
A/Cameroon/9766/2017 H6N1 - Day 57	76.6	76.3	53.6
A/Cameroon/9766/2017 H6N1 - Day 90	69.3	66.6	48.9
A/Cameroon/9766/2017 H6N1 - Day 118	83.1	81.9	62.0
A/Hubeiwujiagang/SWL310/2013 - Day 1	108.5	105.0	92.7
A/Hubeiwujiagang/SWL310/2013 - Day 8	197.7	191.2	167.1
A/Hubeiwujiagang/SWL310/2013 - Day 29	143.3	161.5	128.1
A/Hubeiwujiagang/SWL310/2013 - Day 57	144.2	151.3	117.3
A/Hubeiwujiagang/SWL310/2013 - Day 90	139.8	145.3	113.1
A/Hubeiwujiagang/SWL310/2013 - Day 118	141.2	160.0	130.5
A/Oman/5532/2017 H6N1 - Day 1	37.7	35.1	31.7
A/Oman/5532/2017 H6N1 - Day 8	80.7	100.2	75.3
A/Oman/5532/2017 H6N1 - Day 29	65.9	74.8	54.1
A/Oman/5532/2017 H6N1 - Day 57	63.3	62.1	48.4
A/Oman/5532/2017 H6N1 - Day 90	57.5	53.9	40.4
A/Oman/5532/2017 H6N1 - Day 118	72.7	70.5	54.9
A/Aksaray/4048/2016 H6N2 - Day 1	33.2	45.2	28.5
A/Aksaray/4048/2016 H6N2 - Day 8	72.9	117.5	81.4
A/Aksaray/4048/2016 H6N2 - Day 29	59.5	102.8	62.9
A/Aksaray/4048/2016 H6N2 - Day 57	51.9	90.4	56.6
A/Aksaray/4048/2016 H6N2 - Day 90	60.0	96.1	63.1
A/Aksaray/4048/2016 H6N2 - Day 118	69.9	91.9	68.0
A/Louisiana/13/2017 H6N2 - Day 1	124.2	154.1	126.6
A/Louisiana/13/2017 H6N2 - Day 8	181.6	317.0	216.7
A/Louisiana/13/2017 H6N2 - Day 29	181.6	305.0	201.6
A/Louisiana/13/2017 H6N2 - Day 57	153.2	250.8	183.5
A/Louisiana/13/2017 H6N2 - Day 90	144.6	215.6	157.1
A/Louisiana/13/2017 H6N2 - Day 118	167.9	266.0	212.8

54. Secondary Outcome

Title	Ratio of Geometric Mean Titers (GMTs) of Serum Neuraminidase Inhibition (NAI) Against Heterologous N1 and N2 Neuraminidase (NA) Antigens Between Adjuvanted and Unadjuvanted Study Arms for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. The unadjuvanted Fluzone study arm is considered a reference group for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	37	40
A/Townsville/51/2016 H6N2 - Day 1	1.2	0.9
A/Cameroon/9766/2017 H6N1 - Day 1	1.0	0.8
A/Hubeiwujiagang/SWL310/2013 - Day 1	1.0	0.9
A/Oman/5532/2017 H6N1 - Day 1	0.9	0.8
A/Aksaray/4048/2016 H6N2 - Day 1	1.4	0.9
A/Townsville/51/2016 H6N2 - Day 8	1.5	1.0
A/Cameroon/9766/2017 H6N1 - Day 8	1.1	0.9
A/Hubeiwujiagang/SWL310/2013 - Day 8	1.0	0.8
A/Oman/5532/2017 H6N1 - Day 8	1.2	0.9
A/Aksaray/4048/2016 H6N2 - Day 8	1.6	1.1
A/Townsville/51/2016 H6N2 - Day 29	1.6	1.1
A/Cameroon/9766/2017 H6N1 - Day 29	1.2	0.8
A/Hubeiwujiagang/SWL310/2013 - Day 29	1.1	0.9
A/Oman/5532/2017 H6N1 - Day 29	1.1	0.8
A/Aksaray/4048/2016 H6N2 - Day 29	1.7	1.1
A/Townsville/51/2016 H6N2 - Day 57	1.4	0.9
A/Cameroon/9766/2017 H6N1 - Day 57	1.0	0.7
A/Hubeiwujiagang/SWL310/2013 - Day 57	1.0	0.8
A/Oman/5532/2017 H6N1 - Day 57	1.0	0.8
A/Aksaray/4048/2016 H6N2 - Day 57	1.7	1.1
A/Townsville/51/2016 H6N2 - Day 90	1.5	1.1
A/Cameroon/9766/2017 H6N1 - Day 90	1.0	0.7
A/Hubeiwujiagang/SWL310/2013 - Day 90	1.0	0.8
A/Oman/5532/2017 H6N1 - Day 90	0.9	0.7
A/Aksaray/4048/2016 H6N2 - Day 90	1.6	1.1
A/Townsville/51/2016 H6N2 - Day 118	1.2	0.9
A/Cameroon/9766/2017 H6N1 - Day 118	1.0	0.7
A/Hubeiwujiagang/SWL310/2013 - Day 118	1.1	0.9
A/Oman/5532/2017 H6N1 - Day 118	1.0	0.8
A/Aksaray/4048/2016 H6N2 - Day 118	1.3	1.0
A/Louisiana/13/2017 H6N2 - Day 1	1.2	1.0
A/Louisiana/13/2017 H6N2 - Day 8	1.7	1.2
A/Louisiana/13/2017 H6N2 - Day 29	1.7	1.1
A/Louisiana/13/2017 H6N2 - Day 57	1.6	1.2
A/Louisiana/13/2017 H6N2 - Day 90	1.5	1.1
A/Louisiana/13/2017 H6N2 - Day 118	1.6	1.3

55. Secondary Outcome

Title	Percentage of Participants Achieving Neuraminidase Inhibition (NAI) Titer Seroconversion Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. NAI seroconversion was defined as >4 four-fold rise in post-vaccination antibody titer at Day 8, 29, 57, 90, and 118.
Time Frame	Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Townsville/51/2016 H6N2 - Day 8	17 41.5%	27 73%	25 62.5%
A/Cameroon/9766/2017 H6N1 - Day 8	24 58.5%	32 86.5%	38 95%
A/Hubeiwujiagang/SWL310/2013 - Day 8	17 41.5%	14 37.8%	18 45%
A/Oman/5532/2017 H6N1 - Day 8	27 65.9%	41 110.8%	28 70%
A/Aksaray/4048/2016 H6N2 - Day 8	29 70.7%	38 102.7%	38 95%
A/Louisiana/13/2017 H6N2 - Day 8	10 24.4%	27 73%	10 25%
A/Townsville/51/2016 H6N2 - Day 29	10 24.4%	14 37.8%	5 12.5%
A/Cameroon/9766/2017 H6N1 - Day 29	15 36.6%	22 59.5%	18 45%
A/Hubeiwujiagang/SWL310/2013 - Day 29	5 12.2%	14 37.8%	3 7.5%
A/Oman/5532/2017 H6N1 - Day 29	17 41.5%	19 51.4%	18 45%
A/Aksaray/4048/2016 H6N2 - Day 29	17 41.5%	25 67.6%	33 82.5%
A/Louisiana/13/2017 H6N2 - Day 29	7 17.1%	19 51.4%	13 32.5%
A/Townsville/51/2016 H6N2 - Day 57	8 19.5%	11 29.7%	5 12.5%
A/Cameroon/9766/2017 H6N1 - Day 57	8 19.5%	11 29.7%	5 12.5%
A/Hubeiwujiagang/SWL310/2013 - Day 57	0 0%	8 21.6%	3 7.5%
A/Oman/5532/2017 H6N1 - Day 57	13 31.7%	8 21.6%	11 27.5%
A/Aksaray/4048/2016 H6N2 - Day 57	5 12.2%	19 51.4%	18 45%
A/Louisiana/13/2017 H6N2 - Day 57	3 7.3%	11 29.7%	8 20%
A/Townsville/51/2016 H6N2 - Day 90	2 4.9%	6 16.2%	5 12.5%
A/Cameroon/9766/2017 H6N1 - Day 90	5 12.2%	11 29.7%	3 7.5%
A/Hubeiwujiagang/SWL310/2013 - Day 90	5 12.2%	11 29.7%	3 7.5%
A/Oman/5532/2017 H6N1 - Day 90	10 24.4%	6 16.2%	5 12.5%
A/Aksaray/4048/2016 H6N2 - Day 90	7 17.1%	17 45.9%	24 60%
A/Louisiana/13/2017 H6N2 - Day 90	2 4.9%	6 16.2%	3 7.5%
A/Townsville/51/2016 H6N2 - Day 118	22 53.7%	10 27%	18 45%
A/Cameroon/9766/2017 H6N1 - Day 118	8 19.5%	13 35.1%	15 37.5%
A/Hubeiwujiagang/SWL310/2013 - Day 118	11 26.8%	10 27%	15 37.5%
A/Oman/5532/2017 H6N1 - Day 118	19 46.3%	17 45.9%	18 45%
A/Aksaray/4048/2016 H6N2 - Day 118	25 61%	17 45.9%	32 80%
A/Louisiana/13/2017 H6N2 - Day 118	8 19.5%	10 27%	18 45%

56. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neuraminidase Inhibition (NAI) Titers Against Heterologous N1 and N2 Neuraminidase (NA) Antigens for the Fluzone Study Arms
Description	Blood was collected for NAI assay which was conducted with the heterologous N1 and N2 NA viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, and the geometric mean of the replicate results of each antigen was calculated as that sample's result. Fold-rises from baseline were calculated as the Day 8 (or Day 29, Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid NAI results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.
Measure Participants	41	37	40
A/Townsville/51/2016 H6N2 - Day 8	2.1	2.5	2.4
A/Cameroon/9766/2017 H6N1 - Day 8	2.2	2.5	2.3
A/Hubeiwujiagang/SWL310/2013 - Day 8	1.8	1.8	1.8
A/Oman/5532/2017 H6N1 - Day 8	2.1	2.9	2.4
A/Aksaray/4048/2016 H6N2 - Day 8	2.2	2.6	2.9
A/Louisiana/13/2017 H6N2 - Day 8	1.5	2.1	1.7
A/Townsville/51/2016 H6N2 - Day 29	1.3	1.7	1.6
A/Cameroon/9766/2017 H6N1 - Day 29	1.7	2.0	1.8
A/Hubeiwujiagang/SWL310/2013 - Day 29	1.3	1.6	1.5
A/Oman/5532/2017 H6N1 - Day 29	1.7	2.1	1.8
A/Aksaray/4048/2016 H6N2 - Day 29	1.8	2.2	2.3
A/Louisiana/13/2017 H6N2 - Day 29	1.5	1.9	1.6
A/Townsville/51/2016 H6N2 - Day 57	1.6	1.8	1.7
A/Cameroon/9766/2017 H6N1 - Day 57	1.5	1.6	1.5
A/Hubeiwujiagang/SWL310/2013 - Day 57	1.3	1.4	1.4
A/Oman/5532/2017 H6N1 - Day 57	1.6	1.8	1.7
A/Aksaray/4048/2016 H6N2 - Day 57	1.6	2.0	2.0
A/Louisiana/13/2017 H6N2 - Day 57	1.3	1.6	1.5
A/Townsville/51/2016 H6N2 - Day 90	1.4	1.6	1.7
A/Cameroon/9766/2017 H6N1 - Day 90	1.4	1.4	1.3
A/Hubeiwujiagang/SWL310/2013 - Day 90	1.3	1.4	1.3
A/Oman/5532/2017 H6N1 - Day 90	1.5	1.5	1.4
A/Aksaray/4048/2016 H6N2 - Day 90	1.8	2.0	2.2
A/Louisiana/13/2017 H6N2 - Day 90	1.2	1.3	1.3
A/Townsville/51/2016 H6N2 - Day 118	2.1	2.0	2.1
A/Cameroon/9766/2017 H6N1 - Day 118	1.8	1.7	2.0
A/Hubeiwujiagang/SWL310/2013 - Day 118	1.4	1.6	1.7
A/Oman/5532/2017 H6N1 - Day 118	2.0	2.0	2.2
A/Aksaray/4048/2016 H6N2 - Day 118	2.4	2.0	2.4
A/Louisiana/13/2017 H6N2 - Day 118	1.5	1.7	1.7

57. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Titers Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 1	293.5	535.4	348.3	412.1	388.6	307.9
A/Aksaray/4048/2016 [H3N2] - Day 1	34.2	46.7	40.5	47.1	40.3	40.9
A/Kenya/105/2017 [H3N2] - Day 1	183.2	294.8	218.7	226.8	232.4	217.9
A/Michigan/84/2016 [H3N2] - Day 1	858.5	852.9	616.3	736.5	667.0	624.2
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	830.8	2284.7	1656.1	1212.0	1795.8	1425.2
A/Aksaray/4048/2016 [H3N2] - Day 8	45.4	101.3	65.8	88.2	121.5	86.9
A/Kenya/105/2017 [H3N2] - Day 8	267.6	486.9	312.8	431.4	559.0	505.9
A/Michigan/84/2016 [H3N2] - Day 8	1237.6	1798.5	1088.9	1051.7	852.0	882.3
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	819.1	2083.9	1416.0	1940.2	2359.5	1922.4
A/Aksaray/4048/2016 [H3N2] - Day 29	43.3	70.9	48.9	82.0	107.0	81.4
A/Kenya/105/2017 [H3N2] - Day 29	344.4	698.1	421.4	821.9	983.9	790.8
A/Michigan/84/2016 [H3N2] - Day 29	1232.8	1541.8	1032.4	1424.0	1020.1	1054.4
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	396.0	1000.2	720.2	1086.0	1208.6	1032.9
A/Aksaray/4048/2016 [H3N2] - Day 57	53.7	117.6	61.8	151.8	156.5	140.0
A/Kenya/105/2017 [H3N2] - Day 57	237.7	469.4	283.7	634.0	688.0	517.7
A/Michigan/84/2016 [H3N2] - Day 57	1071.2	1602.1	946.6	1533.4	904.9	1158.3
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	556.7	1501.0	946.6	1331.6	1563.9	1268.5
A/Aksaray/4048/2016 [H3N2] - Day 90	62.4	111.0	64.7	149.1	147.2	129.6
A/Kenya/105/2017 [H3N2] - Day 90	151.6	315.4	200.1	431.5	444.3	385.5
A/Michigan/84/2016 [H3N2] - Day 90	841.2	1268.8	778.8	1297.0	733.5	905.2
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	1128.1	1723.8	1631.8	2739.4	3672.3	2233.2
A/Aksaray/4048/2016 [H3N2] - Day 118	94.6	139.0	150.1	326.1	296.5	241.3
A/Kenya/105/2017 [H3N2] - Day 118	300.7	400.6	369.1	936.6	965.5	733.9
A/Michigan/84/2016 [H3N2] - Day 118	1382.3	1785.2	1487.2	2572.0	1537.3	1641.9

58. Secondary Outcome

Title	Ratio of Serum Neutralizing (Neut) Geometric Mean Titers (GMT) Against Heterologous H1 and H3 Influenza Strains Between Adjuvanted and Unadjuvanted Study Arms
Description	Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. The geometric mean titer was calculated for each study arm from the available results at Day 1, Day 8, Day 29, Day 57, Day 90, and Day 118 Post first study vaccination and the ratio of these GMTs between adjuvanted and unadjuvanted study arms were calculated. Unadjuvanted Fluzone and Flublok study arms are considered as reference groups for the analysis of ratio of GMTs. Ratio of GMTs is defined as the ratio of the GMT from the adjuvanted group divided by the GMT from the corresponding unadjuvanted group.
Time Frame	Day 1, Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone + AF03	Fluzone + CpG55	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	37	40	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 1	1.8	1.2	0.9	0.7
A/Aksaray/4048/2016 [H3N2] - Day 1	1.4	1.2	0.9	0.9
A/Kenya/105/2017 [H3N2] - Day 1	1.6	1.2	1.0	1.0
A/Michigan/84/2016 [H3N2] - Day 1	1.0	0.7	0.9	0.8
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	2.7	2.0	1.5	1.2
A/Aksaray/4048/2016 [H3N2] - Day 8	2.2	1.4	1.4	1.0
A/Kenya/105/2017 [H3N2] - Day 8	1.8	1.2	1.3	1.2
A/Michigan/84/2016 [H3N2] - Day 8	1.5	0.9	0.8	0.8
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	2.5	1.7	1.2	1.0
A/Aksaray/4048/2016 [H3N2] - Day 29	1.6	1.1	1.3	1.0
A/Kenya/105/2017 [H3N2] - Day 29	2.0	1.2	1.2	1.0
A/Michigan/84/2016 [H3N2] - Day 29	1.3	0.8	0.7	0.7
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	2.5	1.8	1.1	1.0
A/Aksaray/4048/2016 [H3N2] - Day 57	2.2	1.2	1.0	0.9
A/Kenya/105/2017 [H3N2] - Day 57	2.0	1.2	1.1	0.8
A/Michigan/84/2016 [H3N2] - Day 57	1.5	0.9	0.6	0.8
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	2.7	1.7	1.2	1.0
A/Aksaray/4048/2016 [H3N2] - Day 90	1.8	1.0	1.0	0.9
A/Kenya/105/2017 [H3N2] - Day 90	2.1	1.3	1.0	0.9
A/Michigan/84/2016 [H3N2] - Day 90	1.5	0.9	0.6	0.7
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	1.5	1.4	1.3	0.8
A/Aksaray/4048/2016 [H3N2] - Day 118	1.5	1.6	0.9	0.7
A/Kenya/105/2017 [H3N2] - Day 118	1.3	1.2	1.0	0.8
A/Michigan/84/2016 [H3N2] - Day 118	1.3	1.1	0.6	0.6

59. Secondary Outcome

Title	Percentage of Participants Achieving Neutralizing (Neut) Titer Seroconversion Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Neut seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and a minimum four-fold rise in post-vaccination antibody titer.
Time Frame	Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	24 58.5%	32 86.5%	33 82.5%	27 65.9%	42 107.7%	45 104.7%
A/Aksaray/4048/2016 [H3N2] - Day 8	7 17.1%	16 43.2%	13 32.5%	20 48.8%	34 87.2%	21 48.8%
A/Kenya/105/2017 [H3N2] - Day 8	12 29.3%	16 43.2%	15 37.5%	15 36.6%	24 61.5%	24 55.8%
A/Michigan/84/2016 [H3N2] - Day 8	12 29.3%	19 51.4%	13 32.5%	10 24.4%	8 20.5%	12 27.9%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	34 82.9%	33 89.2%	31 77.5%	55 134.1%	51 130.8%	49 114%
A/Aksaray/4048/2016 [H3N2] - Day 29	7 17.1%	11 29.7%	5 12.5%	10 24.4%	24 61.5%	17 39.5%
A/Kenya/105/2017 [H3N2] - Day 29	15 36.6%	22 59.5%	21 52.5%	35 85.4%	43 110.3%	39 90.7%
A/Michigan/84/2016 [H3N2] - Day 29	12 29.3%	17 45.9%	10 25%	15 36.6%	11 28.2%	12 27.9%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	15 36.6%	16 43.2%	26 65%	33 80.5%	35 89.7%	32 74.4%
A/Aksaray/4048/2016 [H3N2] - Day 57	13 31.7%	14 37.8%	11 27.5%	38 92.7%	49 125.6%	37 86%
A/Kenya/105/2017 [H3N2] - Day 57	8 19.5%	19 51.4%	16 40%	30 73.2%	32 82.1%	29 67.4%
A/Michigan/84/2016 [H3N2] - Day 57	13 31.7%	16 43.2%	3 7.5%	13 31.7%	8 20.5%	12 27.9%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	20 48.8%	25 67.6%	24 60%	33 80.5%	41 105.1%	40 93%
A/Aksaray/4048/2016 [H3N2] - Day 90	17 41.5%	17 45.9%	11 27.5%	33 80.5%	49 125.6%	30 69.8%
A/Kenya/105/2017 [H3N2] - Day 90	5 12.2%	8 21.6%	8 20%	18 43.9%	22 56.4%	18 41.9%
A/Michigan/84/2016 [H3N2] - Day 90	0 0%	8 21.6%	3 7.5%	10 24.4%	8 20.5%	8 18.6%
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	47 114.6%	33 89.2%	44 110%	56 136.6%	72 184.6%	68 158.1%
A/Aksaray/4048/2016 [H3N2] - Day 118	33 80.5%	27 73%	35 87.5%	79 192.7%	69 176.9%	62 144.2%
A/Kenya/105/2017 [H3N2] - Day 118	19 46.3%	10 27%	21 52.5%	44 107.3%	44 112.8%	38 88.4%
A/Michigan/84/2016 [H3N2] - Day 118	19 46.3%	17 45.9%	18 45%	32 78%	22 56.4%	35 81.4%

60. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) in Neutralizing (Neut) Titers Against Heterologous H1 and H3 Influenza Strains
Description	Blood was collected for Neut assay which was conducted with the heterologous H1 and H3 influenza viruses as the antigens. Each sample was tested twice per antigen per the laboratory's standard operating procedure, but only one result which a geometric mean titer of the replicates was reported by the lab. Fold-rises from baseline were calculated as the Day 8 (or Day 29, Day 57, Day 90, Day 118) titer divided by the baseline titers for each participant. The geometric mean of these fold rises was then calculated to obtain the GMFR.
Time Frame	Day 8, Day 29, Day 57, Day 90, Day 118

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population includes all randomized participants who received the first study vaccination and contributed at least one post-first study vaccination venous blood samples for immunogenicity testing (HAI, NAI or Neut antibody assays) for which valid Neut results were reported. For analyses using the mITT population, participants were grouped based on randomized study arm.

Arm/Group Title	Fluzone	Fluzone + AF03	Fluzone + CpG55	Flublok	Flublok + AF03	Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.	0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
Measure Participants	41	37	40	41	38	42
A/Shandonglaicheng/1763/2016 [H3N2] - Day 8	2.8	4.3	4.8	2.9	4.6	4.6
A/Aksaray/4048/2016 [H3N2] - Day 8	1.3	2.2	1.6	1.9	3.0	2.1
A/Kenya/105/2017 [H3N2] - Day 8	1.5	1.7	1.4	1.9	2.4	2.3
A/Michigan/84/2016 [H3N2] - Day 8	1.4	2.1	1.8	1.4	1.3	1.4
A/Shandonglaicheng/1763/2016 [H3N2] - Day 29	2.8	3.4	4.3	4.7	5.5	5.9
A/Aksaray/4048/2016 [H3N2] - Day 29	1.3	1.5	1.2	1.7	2.6	2.0
A/Kenya/105/2017 [H3N2] - Day 29	1.9	2.3	1.9	3.6	4.1	3.5
A/Michigan/84/2016 [H3N2] - Day 29	1.4	1.8	1.6	1.9	1.5	1.7
A/Shandonglaicheng/1763/2016 [H3N2] - Day 57	1.4	1.9	2.3	2.6	3.0	3.2
A/Aksaray/4048/2016 [H3N2] - Day 57	1.6	2.5	1.6	3.2	3.8	3.4
A/Kenya/105/2017 [H3N2] - Day 57	1.3	1.6	1.3	2.7	2.9	2.3
A/Michigan/84/2016 [H3N2] - Day 57	1.3	1.9	1.5	2.0	1.4	1.8
A/Shandonglaicheng/1763/2016 [H3N2] - Day 90	1.9	2.5	3.0	3.3	3.8	3.8
A/Aksaray/4048/2016 [H3N2] - Day 90	1.8	2.3	1.6	3.1	3.5	3.1
A/Kenya/105/2017 [H3N2] - Day 90	0.8	1.0	0.9	1.9	1.9	1.7
A/Michigan/84/2016 [H3N2] - Day 90	1.0	1.5	1.3	1.7	1.1	1.4
A/Shandonglaicheng/1763/2016 [H3N2] - Day 118	4.6	2.8	5.7	6.8	9.9	7.8
A/Aksaray/4048/2016 [H3N2] - Day 118	3.0	2.9	3.7	6.9	7.3	6.1
A/Kenya/105/2017 [H3N2] - Day 118	1.8	1.2	1.8	4.2	4.2	3.5
A/Michigan/84/2016 [H3N2] - Day 118	1.7	1.8	2.4	3.2	2.3	2.6

Adverse Events

Time Frame	Serious Adverse Events (SAEs), AESIs (including protocol-specified AESIs, MAAEs, NOCMCs and PIMMCs) were collected from the time of first study vaccination through approximately 12 months following first study vaccination. Solicited Adverse Events (AEs) and clinical safety laboratory AEs were collected from the time of first study vaccination through Day 7. Non-serious, unsolicited AEs were collected from the time of first study vaccination through approximately Day 29.
Adverse Event Reporting Description	Solicited AEs include injection site reactions and systemic reactions. Injection site reactions include pruritus, ecchymosis, erythema, induration, edema, pain, and tenderness. Systemic reactions include fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and nausea.
Arm/Group Title	Fluzone		Fluzone + AF03		Fluzone + CpG55		Flublok		Flublok + AF03		Flublok + CpG55
Arm/Group Description	0.5 mL of 2018/2019 Fluzone QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.		0.5 mL of 2018/2019 Fluzone QIV + 0.25 mL of AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Fluzone QIV intramuscular injection on Day 90.		0.5 mL of 2018/2019 Fluzone QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 2019/2020 of Fluzone QIV intramuscular injection on Day 90.		0.5 mL of 2018/2019 Flublok QIV intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.		0.5 mL of 2018/2019 Flublok QIV + 0.25 mL AF03 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90. One participant randomized to the Flublok + AF03 arm received Flublok due to a pharmacy error and is analyzed in the Flublok group for safety-related analyses.		0.5 mL of 2018/2019 Flublok QIV + 0.5 mL of Delta Inulin-CpG55.2 (admixed with vaccine) intramuscular injection on Day 1 and 0.5 ml of 2019/2020 Flublok QIV intramuscular injection on Day 90.
All Cause Mortality
	Fluzone		Fluzone + AF03		Fluzone + CpG55		Flublok		Flublok + AF03		Flublok + CpG55
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/37 (0%)		0/40 (0%)		0/42 (0%)		0/37 (0%)		0/43 (0%)
Serious Adverse Events
	Fluzone		Fluzone + AF03		Fluzone + CpG55		Flublok		Flublok + AF03		Flublok + CpG55
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		1/37 (2.7%)		0/40 (0%)		0/42 (0%)		0/37 (0%)		1/43 (2.3%)
Infections and infestations
Clostridium Difficile Colitis	0/41 (0%)	0	1/37 (2.7%)	1	0/40 (0%)	0	0/42 (0%)	0	0/37 (0%)	0	0/43 (0%)	0
Musculoskeletal and connective tissue disorders
Chronic Left Knee Pain	0/41 (0%)	0	0/37 (0%)	0	0/40 (0%)	0	0/42 (0%)	0	0/37 (0%)	0	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Fluzone		Fluzone + AF03		Fluzone + CpG55		Flublok		Flublok + AF03		Flublok + CpG55
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/41 (90.2%)		36/37 (97.3%)		40/40 (100%)		36/42 (85.7%)		34/37 (91.9%)		43/43 (100%)
Gastrointestinal disorders
Diarrhoea	1/41 (2.4%)	1	3/37 (8.1%)	3	0/40 (0%)	0	1/42 (2.4%)	1	2/37 (5.4%)	2	0/43 (0%)	0
Nausea	2/41 (4.9%)	2	3/37 (8.1%)	3	3/40 (7.5%)	3	5/42 (11.9%)	5	5/37 (13.5%)	5	6/43 (14%)	6
General disorders
Fatigue	13/41 (31.7%)	13	16/37 (43.2%)	16	14/40 (35%)	14	13/42 (31%)	13	14/37 (37.8%)	14	15/43 (34.9%)	15
Influenza like illness	0/41 (0%)	0	0/37 (0%)	0	2/40 (5%)	2	1/42 (2.4%)	1	0/37 (0%)	0	0/43 (0%)	0
Malaise	9/41 (22%)	9	11/37 (29.7%)	11	8/40 (20%)	8	6/42 (14.3%)	6	8/37 (21.6%)	8	5/43 (11.6%)	5
Pyrexia	3/41 (7.3%)	3	4/37 (10.8%)	4	6/40 (15%)	6	5/42 (11.9%)	5	5/37 (13.5%)	5	4/43 (9.3%)	4
Vaccination site bruising	2/41 (4.9%)	2	3/37 (8.1%)	3	1/40 (2.5%)	1	2/42 (4.8%)	2	0/37 (0%)	0	4/43 (9.3%)	4
Vaccination site erythema	8/41 (19.5%)	8	9/37 (24.3%)	9	16/40 (40%)	16	6/42 (14.3%)	6	7/37 (18.9%)	7	12/43 (27.9%)	12
Vaccination site induration	12/41 (29.3%)	12	4/37 (10.8%)	4	13/40 (32.5%)	13	6/42 (14.3%)	6	6/37 (16.2%)	6	13/43 (30.2%)	13
Vaccination site pain	12/41 (29.3%)	12	22/37 (59.5%)	22	26/40 (65%)	26	7/42 (16.7%)	7	21/37 (56.8%)	21	27/43 (62.8%)	27
Vaccination site pain (tenderness)	29/41 (70.7%)	29	35/37 (94.6%)	35	38/40 (95%)	38	30/42 (71.4%)	30	30/37 (81.1%)	30	41/43 (95.3%)	41
Vaccination site pruritus	1/41 (2.4%)	1	1/37 (2.7%)	1	1/40 (2.5%)	1	1/42 (2.4%)	1	1/37 (2.7%)	1	3/43 (7%)	3
Infections and infestations
Pharyngitis streptococcal	0/41 (0%)	0	2/37 (5.4%)	2	0/40 (0%)	0	0/42 (0%)	0	0/37 (0%)	0	1/43 (2.3%)	1
Upper respiratory tract infection	0/41 (0%)	0	1/37 (2.7%)	1	1/40 (2.5%)	1	1/42 (2.4%)	1	4/37 (10.8%)	4	0/43 (0%)	0
Urinary tract infection	1/41 (2.4%)	1	2/37 (5.4%)	2	1/40 (2.5%)	2	0/42 (0%)	0	1/37 (2.7%)	1	0/43 (0%)	0
Investigations
Aspartate aminotransferase increased	0/41 (0%)	0	1/37 (2.7%)	2	0/40 (0%)	0	1/42 (2.4%)	1	2/37 (5.4%)	2	1/43 (2.3%)	2
Haemoglobin decreased	1/41 (2.4%)	1	1/37 (2.7%)	1	2/40 (5%)	3	4/42 (9.5%)	6	0/37 (0%)	0	0/43 (0%)	0
Platelet count increased	0/41 (0%)	0	0/37 (0%)	0	0/40 (0%)	0	4/42 (9.5%)	8	0/37 (0%)	0	0/43 (0%)	0
White blood cell count decreased	6/41 (14.6%)	6	3/37 (8.1%)	3	3/40 (7.5%)	3	2/42 (4.8%)	2	3/37 (8.1%)	3	0/43 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/41 (4.9%)	2	5/37 (13.5%)	5	1/40 (2.5%)	1	3/42 (7.1%)	3	1/37 (2.7%)	1	2/43 (4.7%)	2
Myalgia	11/41 (26.8%)	11	15/37 (40.5%)	15	12/40 (30%)	12	6/42 (14.3%)	6	9/37 (24.3%)	9	11/43 (25.6%)	11
Nervous system disorders
Headache	11/41 (26.8%)	12	21/37 (56.8%)	21	10/40 (25%)	10	13/42 (31%)	13	11/37 (29.7%)	11	10/43 (23.3%)	10
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/41 (0%)	0	1/37 (2.7%)	1	0/40 (0%)	0	0/42 (0%)	0	0/37 (0%)	0	3/43 (7%)	3

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.