Safety of and Immune Response to an H1N1 Influenza Virus Vaccine in HIV Infected Children and Youth

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00992836
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 155
• Locations: 37
• Arm: 1
• Duration (Months): 10
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Children and people infected with HIV are particularly susceptible to influenza infections. This study testED the safety and effectiveness of a vaccine for the new H1N1 influenza virus in children and youth infected with HIV.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; H1N1 Influenza Virus	Biological: Influenza A (H1N1) 2009 monovalent vaccine	Phase 2

Detailed Description

The new H1N1 influenza virus seen in 2009 has been designated a pandemic by the World Health Organization, due to the sustained community outbreaks seen in the United States and Mexico. Based on preliminary data, it appears children and young adults were particularly at risk of the H1N1 virus. People infected with HIV were also more susceptible to severe influenza infections than those who are uninfected. Children with HIV infection, then, have a compounded risk of H1N1 infection. Higher doses of influenza vaccines are associated with the development of higher levels of serum antibodies, which are needed to resist infection. Higher vaccine doses can be used to improve vaccine effectiveness in at-risk populations. This study tested the safety and immune response of HIV infected children and youth to a high dose of a vaccine for the new H1N1 influenza virus.

Participation in this study lasted 7 months and had two steps. The first step involved receiving the first dose of H1N1 virus vaccine, and the second step, occurring 21 days later, involved receiving the second dose of vaccine. Each dose of vaccine was delivered via two intramuscular shots (four total injections). After receiving each dose of the vaccine, participants were given a diary to record any symptoms or reactions. Participants were stratified into three groups by age, including 4 to 9 years, 9 to 18 years, and 18 to 25 years.

Participants completed five scheduled visits, taking place at screening, study entry, Days 21 and 31, and after 7 months. Measurements taken on these visits included a medical history, physical and neurological exams, a blood draw, and, when applicable, a pregnancy test. In addition to these visits, participants received up to three additional phone calls or visits occurring 2 and 10 days after the first dose of vaccine and 2 days after the second dose of vaccine to check for reactions to the vaccine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II Study to Assess the Safety and Immunogenicity of an Inactivated Swine-Origin H1N1 Influenza Vaccine in HIV-1 Perinatally Infected Children and Youth
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Influenza A (H1N1) 2009 monovalent vaccine All participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart.	Biological: Influenza A (H1N1) 2009 monovalent vaccine; Two doses of vaccine, delivered 21 days apart, with each dose consisting of two 15-microgram intramuscular injections

Outcome Measures

Primary Outcome Measures

1. The Number of Participants Who Had at Least One Adverse Event (AE) [Measured up to 7 months after vaccination]

   Shows the number of participants who had at least one adverse event (AE) in each category. The AEs include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

2. The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine [Measured up to 7 months after vaccination]

   Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

3. Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose [Measured at Day 21]

4. Percent of Participants With a Hemagglutinin Inhibition (HAI) Titer of >=40 [Measured at 21 days after first dose and 10 days after second dose]

   Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640 and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.

Secondary Outcome Measures

1. Percent of Participants With an HAI Titer >=40 at Long-term Follow-up [Measured at 6 months after second dose]

2. Geometric Mean Antibody Titers (GMT) HAI [Measured after first and second doses and 6 months after second dose]

   Presents the value of the geometric mean titer at each time point.

3. Cell-mediated Immune Responses, Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values [Measured at entry, 21 days after first dose, and 10 days after second dose]

   The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 peripheral blood mononucleated cell (PBMC) and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.

4. HAI Titers Against Seasonal Influenza Viruses Containing Trivalent Influenza Vaccine (TIV) [Measured at entry, 21 days after first dose, and 10 days and 6 months after second dose]

   Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.

5. Cell-mediated Immune Responses to Influenza Viruses Contained in TIV and Other Antigens [Measured at entry, 21 days after first dose, and 10 days after second dose]

   The TIV assay was not performed due to lack of available cells after completion of other planned assays. The median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 Granzyme B spot-forming cells (SFC)/10^6 peripheral blood mononucleated cell (PBMC). The median and interquartile range (IQR) of T-Cell ELISPOT-measured PHA INFgamma spot-forming cells (SFC)/10^6 PBMC. The median and interquartile range (IQR) of T-Cell ELISPOT-measured PHA Granzyme B spot-forming cells (SFC)/10^6 PBMC.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for Step I:

• HIV infected

• HIV-1 was perinatally acquired, in the opinion of the investigator

• Participants receiving antiretrovirals (ARVs) must have been receiving a stable regimen for 90 days prior to entry with no intention to modify their regimen within 60 days following study entry

• Participants not receiving ARVs at entry must not have received ARVs within 90 days prior to entry and must NOT plan to initiate ARVs within 60 days following study entry

• Ability to complete all study immunizations and evaluations, in the opinion of the investigator

• Agrees to use contraception, if necessary

• Documented platelet count of more than 50,000 per mm3 and an absolute neutrophil count (ANC) of more than 500 per mm3 within the 30 days prior to study entry

• Youth of legal age (from 18 to 25 years of age), parent or legal guardian, or participants who are emancipated minors must provide informed consent

Inclusion Criteria for Step II:

• Received the first dose of Influenza A (H1N1) 2009 monovalent vaccine at least 21 days ago

• Documented platelet count of more than 50,000 per mm3 and an ANC of more than 500 per mm3 within the 30 days prior to Step II entry

• If a woman became pregnant after Dose #1, she must be at more than 14 weeks of gestation and have her obstetrician's permission to receive the vaccine

Exclusion Criteria for Step I:

• Pregnancy

• Known allergy to egg protein (egg or egg product) or other components in the vaccines (these may include, but are not limited to: neomycin and polymyxin)

• History, in the opinion of the site investigator, of severe reactions following previous immunization with seasonal influenza vaccines that would contraindicate receipt of any influenza vaccine.

• History of probable or proven pandemic 2009 Influenza A (H1N1) infection prior to study entry

• Has received any live licensed vaccine within 4 weeks or inactivated licensed vaccine within 2 weeks prior to study entry

• Has received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication) within 4 weeks prior to study entry or expects to receive another nonlicensed agent during the course of the study

• Has an acute illness or a documented temperature greater than or equal to 100.0 degrees Fahrenheit within 24 hours prior to study entry

• Use of anti-cancer chemotherapy or radiation therapy within the 36 months preceding study entry or has immunosuppression as a result of an underlying illness or treatment (other than HIV-1 infection)

• Has an active neoplastic disease

• Long-term use of glucocorticoids, including oral or parenteral prednisone or equivalent (at least 2 mg/kg per day or at least 20 mg total dose) for more than 2 weeks in the past 6 months or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. Nasal and topical steroids are allowed.

• Has received immunoglobulin or other blood products within the 3 months prior to study entry

• History of Guillain-Barre syndrome in the subject or subject's family, including parents, siblings, half-siblings, and children

• Onset of a neurological disorder including (but not limited to) absent ankle and patellar deep tendon reflexes in both legs (all four absent) within the past 6 months

• Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities within the past 6 months

• Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol

Exclusion Criteria for Step II:

• Has received a nonlicensed agent (vaccine, drug, biologic, device, blood product, or medication), other than from participation in this study, since Dose #1 or expects to receive another nonlicensed agent before the end of the study

• Use of anti-cancer chemotherapy or radiation therapy since Dose #1, new diagnosis of an active malignancy, or is immunosuppressed as a result of an underlying illness (other than HIV-1 infection) or treatment.

• Use of glucocorticoids, including oral or parenteral steroids (at least 2 mg/kg per day or at least 20 mg total dose) for more than 2 weeks since vaccine Dose #1 or high-dose inhaled steroids (more than 800 mcg/day of beclomethasone dipropionate or equivalent) since Dose #1 (nasal and topical steroids are allowed)

• Has received immunoglobulin or other blood products since Dose #1

• Any Grade 3 toxicity or adverse event (AE) experienced by a participant, unless the investigator has received protocol team approval

• Any Grade 4 toxicity or AE (other than injection site reaction or fever) that is definitely, probably or possibly related to study vaccine

• Any Grade 4 injection site reactions or fever experienced by a participant, unless the investigator has received protocol team approval

• Any Grade 4 AEs that are definitely not or probably not related to study vaccine, unless the investigator has received protocol team approval

• New occurrence or new awareness of Guillain-Barre syndrome in the participant or participant's family (parents, siblings, half-siblings, or children) since Dose #1

• New onset of a neurological disorder including (but not limited to) absent ankle and patellar deep tendon reflexes in both legs (all four absent) since Dose #1

• Disproportionate loss of strength in lower extremity or extremities compared to the upper extremities (not thought to be related to pregnancy) since Dose #1

• Documented infection with 2009 Influenza A (H1N1) since Dose #1

• Refusal of further vaccination by participant, parent, or guardian

• Development of any new disease that the investigator judges to be clinically significant or clinically significant findings since Dose #1 that, in the investigator's opinion, would compromise the safety of the subject

• Withdrawal of consent. Consent may be withdrawn at any time and for any reason, without penalty.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Pediatric Infectious Diseases CRS	Birmingham	Alabama	United States	35233
2	Usc La Nichd Crs	Alhambra	California	United States	91803
3	University of California, UC San Diego CRS	La Jolla	California	United States	92093-0672
4	Miller Children's Hosp. Long Beach CA NICHD CRS	Long Beach	California	United States	90806
5	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California	United States	90095-1752
6	Univ. of California San Francisco NICHD CRS	San Francisco	California	United States	94143
7	Harbor UCLA Medical Ctr. NICHD CRS	Torrance	California	United States	90502
8	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado	United States	80045
9	Children's National Med. Ctr. Washington DC NICHD CRS	Washington	District of Columbia	United States	20010
10	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia	United States	20060
11	South Florida CDTC Ft Lauderdale NICHD CRS	Fort Lauderdale	Florida	United States	33316
12	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida	United States	32209
13	Pediatric Perinatal HIV Clinical Trials Unit CRS	Miami	Florida	United States	33136
14	USF - Tampa NICHD CRS	Tampa	Florida	United States	33606
15	Rush Univ. Cook County Hosp. Chicago NICHD CRS	Chicago	Illinois	United States	60612
16	Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS	Chicago	Illinois	United States	60614-3393
17	Univ. of Maryland Baltimore NICHD CRS	Baltimore	Maryland	United States	21201
18	Johns Hopkins Univ. Baltimore NICHD CRS	Baltimore	Maryland	United States	21287
19	Children's Hosp. of Boston NICHD CRS	Boston	Massachusetts	United States	02115
20	Boston Medical Center Ped. HIV Program NICHD CRS	Boston	Massachusetts	United States	02118
21	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts	United States	01605
22	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan	United States	48201
23	Rutgers - New Jersey Medical School CRS	Newark	New Jersey	United States	01703
24	Bronx-Lebanon CRS	Bronx	New York	United States	10457
25	Jacobi Med. Ctr. Bronx NICHD CRS	Bronx	New York	United States	10461
26	Nyu Ny Nichd Crs	New York	New York	United States	10016
27	Metropolitan Hosp. NICHD CRS	New York	New York	United States	10029
28	Columbia IMPAACT CRS	New York	New York	United States	10032
29	Strong Memorial Hospital Rochester NY NICHD CRS	Rochester	New York	United States	14642
30	SUNY Stony Brook NICHD CRS	Stony Brook	New York	United States	11794-8111
31	DUMC Ped. CRS	Durham	North Carolina	United States	27710
32	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania	United States	19104
33	St. Jude Children's Research Hospital CRS	Memphis	Tennessee	United States	38105-3678
34	Texas Children's Hospital CRS	Houston	Texas	United States	77030-2399
35	Seattle Children's Research Institute CRS	Seattle	Washington	United States	98101
36	University of Puerto Rico Pediatric HIV/AIDS Research Program CRS	San Juan		Puerto Rico	00935
37	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico	00936

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Chair: Pat Flynn, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for information on the IMPAACT group and for the package insert on the H1N1 vaccine.
• Click here for the table used for grading toxicities: DAIDS Grading Severity of AEs, V1.0, Dec04.

Publications

• Gelinck LB, van den Bemt BJ, Marijt WA, van der Bijl AE, Visser LG, Cats HA, Rimmelzwaan GF, Kroon FP. Intradermal influenza vaccination in immunocompromized patients is immunogenic and feasible. Vaccine. 2009 Apr 21;27(18):2469-74. doi: 10.1016/j.vaccine.2009.02.053. Epub 2009 Feb 24.
• Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009 Jun 18;360(25):2605-15. doi: 10.1056/NEJMoa0903810. Epub 2009 May 7. Erratum in: N Engl J Med. 2009 Jul 2;361(1):102.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00992836
• Other Study ID Numbers: P1088; 10840; IMPAACT P1088
• First Posted: Oct 9, 2009
• Last Update Posted: Nov 5, 2021
• Last Verified: Dec 1, 2014

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Influenza A Virus, H1N1 Subtype; Vaccine; Children; Adolescents; HIV-Infected; Perinatal HIV Infection; Treatment experienced
• Additional relevant MeSH terms: Influenza, Human; HIV Infections

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 37 sites between October 14, 2009 and November 12, 2009. Participants were stratified by age in three groups: >=4 to < 9 years old, >=9 to < 18 years old and >=18 to <25 years old.
Pre-assignment Detail	One study participant was inadvertently enrolled with acute illness, was not given any vaccination and was immediately taken off study. A second study participant received the first vaccination but it was discovered that he/she was not compliant with the ARV regimen and was taken off study before receiving the second dose of vaccine.

Arm/Group Title	All Study Participants
Arm/Group Description	Participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Period Title: Overall Study
STARTED	155
Received Both Study Vaccinations	150
COMPLETED	150
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Overall Participants	155
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13 (6)
Sex: Female, Male (Count of Participants)
Female	76 49%
Male	79 51%
Region of Enrollment (participants) [Number]
United States	147 94.8%
Puerto Rico	8 5.2%
Age Strata (Number) [Number]
>=4 to < 9 years old	54 34.8%
>=9 to < 18 years old	51 32.9%
>=18 to < 25 years old	50 32.3%
CD4 Cells Count (cells / mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells / mm^3]	568 (242)
Percentage of CD4 Cells (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	29 (11)

Outcome Measures

1. Primary Outcome

Title	The Number of Participants Who Had at Least One Adverse Event (AE)
Description	Shows the number of participants who had at least one adverse event (AE) in each category. The AEs include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame	Measured up to 7 months after vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Study Participants
Arm/Group Description	All 155 study participants are included in this analysis.
Measure Participants	155
Overall (New AEs after start of treatment)	113 72.9%
Grade 4 AEs (New, after start of treatment)	0 0%
Grade 3 AEs (New, after start of treatment)	7 4.5%
Grade 2 local and systemic AEs to injection	6 3.9%

2. Primary Outcome

Title	The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine
Description	Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame	Measured up to 7 months after vaccination

Outcome Measure Data

Analysis Population Description

The 154 study participants who received at last one vaccination are included in this analysis.

Arm/Group Title	Vaccinated Study Participants
Arm/Group Description	The 154 study participants who received at last one vaccination are included in this analysis.
Measure Participants	154
Number [participants]	7 4.5%

3. Primary Outcome

Title	Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose
Time Frame	Measured at Day 21

Outcome Measure Data

Analysis Population Description

The 154 study participants who received at last one vaccination are included in this analysis.

Arm/Group Title	Vaccinated Study Participants
Arm/Group Description	The 154 study participants who received at last one vaccination are included in this analysis.
Measure Participants	154
Number [participants]	0 0%

4. Primary Outcome

Title	Percent of Participants With a Hemagglutinin Inhibition (HAI) Titer of >=40
Description	Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640 and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame	Measured at 21 days after first dose and 10 days after second dose

Outcome Measure Data

Analysis Population Description

The HAI titers following the first vaccination were summarized for the eligible study participants who received at least one vaccine and had nonmissing HAI data, and the titers following the second vaccination for the eligible study participants who received both doses of vaccine and had nonmissing HAI data.

Arm/Group Title	Overall
Arm/Group Description	The total N for these analyses were 140 and 142, for the analysis of antibody titers after the first and second vaccinations, respectively.
Measure Participants	142
Post dose 1 (N=140)	72.1 46.5%
Post dose 2 (N=142)	82.4 53.2%

5. Secondary Outcome

Title	Percent of Participants With an HAI Titer >=40 at Long-term Follow-up
Time Frame	Measured at 6 months after second dose

Outcome Measure Data

Analysis Population Description

The HAI titers were summarized for the eligible study participants who received both doses of vaccine and had nonmissing HAI data.

Arm/Group Title	Overall
Arm/Group Description	The total N for this analysis was 138, those who received both vaccinations and had nonmissing data.
Measure Participants	138
Number (95% Confidence Interval) [percentage of participants]	57.2 36.9%

6. Secondary Outcome

Title	Geometric Mean Antibody Titers (GMT) HAI
Description	Presents the value of the geometric mean titer at each time point.
Time Frame	Measured after first and second doses and 6 months after second dose

Outcome Measure Data

Analysis Population Description

The HAI titers following the first vaccination were summarized for the eligible study participants who received at least one vaccine and had nonmissing HAI data, and the titers following the second vaccination for the eligible study participants who received both doses of vaccine and had nonmissing HAI data.

Arm/Group Title	Overall
Arm/Group Description	The total N for these analyses were 140, 142 and 138, for the analysis of antibody titers after the first and second vaccinations and after 6 months after the second vaccination, respectively.
Measure Participants	142
At 21 days after the first vaccination (N=140)	85
At 10 days after the second vaccination (N=142)	127
At 6 months after the second vaccination (N=138)	33

7. Secondary Outcome

Title	Cell-mediated Immune Responses, Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values
Description	The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 peripheral blood mononucleated cell (PBMC) and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.
Time Frame	Measured at entry, 21 days after first dose, and 10 days after second dose

Outcome Measure Data

Analysis Population Description

The participants who had received all doses of vaccine up to that timepoint and had sufficient samples for testing.

Arm/Group Title	Overall
Arm/Group Description	The total N for this analysis was 68, those who received the vaccinations and had enough samples for testing.
Measure Participants	68
IgG ASC/10^6 PBMC, Week 0 (N=46)	6
IgG ASC/10^6 PBMC, Post Dose 1 (N=40)	13
IgG ASC/10^6 PBMC, Post Dose 2 (N=40)	12
pH1N1 IFNgamma SFC/10^6 PBMC, Week 0 (N=68)	317
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 1 (N=68)	363
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 2 (N=65)	261

8. Secondary Outcome

Title	HAI Titers Against Seasonal Influenza Viruses Containing Trivalent Influenza Vaccine (TIV)
Description	Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame	Measured at entry, 21 days after first dose, and 10 days and 6 months after second dose

Outcome Measure Data

Analysis Population Description

The participants who had received all doses of vaccine up to that timepoint and had sufficient samples for testing.

Arm/Group Title	Influenza A (H1N1) 2009 Monovalent Vaccine
Arm/Group Description	All participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Influenza A (H1N1) 2009 monovalent vaccine: Two doses of vaccine, delivered 21 days apart, with each dose consisting of two 15-microgram intramuscular injections
Measure Participants	123
Week 0 (N=123)	40
Post Dose 1 (N=121)	40
Post Dose 2 (N=121)	40
6 months Post Dose 2 (N=122)	40

9. Secondary Outcome

Title	Cell-mediated Immune Responses to Influenza Viruses Contained in TIV and Other Antigens
Description	The TIV assay was not performed due to lack of available cells after completion of other planned assays. The median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 Granzyme B spot-forming cells (SFC)/10^6 peripheral blood mononucleated cell (PBMC). The median and interquartile range (IQR) of T-Cell ELISPOT-measured PHA INFgamma spot-forming cells (SFC)/10^6 PBMC. The median and interquartile range (IQR) of T-Cell ELISPOT-measured PHA Granzyme B spot-forming cells (SFC)/10^6 PBMC.
Time Frame	Measured at entry, 21 days after first dose, and 10 days after second dose

Outcome Measure Data

Analysis Population Description

The participants who had received all doses of vaccine up to that timepoint and had sufficient samples for testing.

Arm/Group Title	Overall
Arm/Group Description	The total N for this analysis was 68, those who received the vaccinations and had enough samples for testing.
Measure Participants	68
pH1N1 Granzyme B SFC/10^6 PBMC, Week 0 (N=64)	35
pH1N1 Granzyme B SFC/10^6 PBMC, Week 3 (N=62)	26
pH1N1 Granzyme B SFC/10^6 PBMC, Week 5 (N=61)	30
PHA INFgamma SFC/10^6 PBMC, Week 0 (N=68)	699
PHA INFgamma SFC/10^6 PBMC, Week 3 (N=68)	637
PHA INFgamma SFC/10^6 PBMC, Week 5 (N=65)	624
PHA Granzyme B SFC/10^6 PBMC, Week 0 (N=64)	3250
PHA Granzyme B SFC/10^6 PBMC, Week 3 (N=62)	3340
PHA Granzyme B SFC/10^6 PBMC, Week 5 (N=60)	2045

Adverse Events

Time Frame	Adverse events were collected from the date of enrollment in the study until 6 months after second vaccination.
Adverse Event Reporting Description	Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Arm/Group Title	All Study Participants
Arm/Group Description	Participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
All Cause Mortality
	All Study Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	6/155 (3.9%)
Blood and lymphatic system disorders
Neutropenia	1/155 (0.6%)
General disorders
Gait disturbance	1/155 (0.6%)
Infections and infestations
Herpes zoster	1/155 (0.6%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/155 (0.6%)
Nervous system disorders
Syncope	1/155 (0.6%)
VIIth nerve paralysis	1/155 (0.6%)
Other (Not Including Serious) Adverse Events
	All Study Participants
	Affected / at Risk (%)	# Events
Total	113/155 (72.9%)
Ear and labyrinth disorders
Ear pain	10/155 (6.5%)
Gastrointestinal disorders
Abdominal pain	11/155 (7.1%)
Diarrhoea	16/155 (10.3%)
Nausea	12/155 (7.7%)
Vomiting	18/155 (11.6%)
General disorders
Adverse event	20/155 (12.9%)
Fatigue	11/155 (7.1%)
Pyrexia	19/155 (12.3%)
Infections and infestations
Otitis media	11/155 (7.1%)
Investigations
Alanine aminotransferase increased	11/155 (7.1%)
Aspartate aminotransferase increased	9/155 (5.8%)
Neutrophil count decreased	21/155 (13.5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	12/155 (7.7%)
Nervous system disorders
Headache	29/155 (18.7%)
Respiratory, thoracic and mediastinal disorders
Cough	51/155 (32.9%)
Nasal congestion	35/155 (22.6%)
Oropharyngeal pain	32/155 (20.6%)
Rhinorrhoea	19/155 (12.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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