Healthy Participants
Conditions
Keywords
Children, Vitamin Supplements, Influenza virus vaccine
Brief summary
Children are particularly vulnerable to respiratory virus infections, especially influenza. Vitamin A & D deficiencies are associated with vulnerability to infectious diseases of the respiratory tract. The central hypothesis of this protocol is that vitamin supplements will enhance antibody responses toward the flu vaccine in children. Children, 2-8 years old, will be randomized to receive influenza virus vaccine with a vitamin A+D supplement or influenza virus vaccine with placebo. Children will be tested for vitamin levels and immune responses before and after influenza virus vaccinations to determine if vitamin supplementation improves the influenza virus vaccine-induced immune response. PRIMARY OBJECTIVE: * To assess the vaccine-induced and total antibody (including IgG and IgA) response after influenza virus vaccine administration and IgA/IgG plus IgA/IgM ratios at 28 and 56 days in sera SECONDARY OBJECTIVE: * To assess the neutralizing response toward influenza virus vaccine in the sera.
Detailed description
Participants will be randomized to receive either an influenza virus vaccine plus Vitamins A & D or an influenza virus vaccine plus placebo. They will be stratified based on retinol binding protein (RBP) levels at screening, using a cut-off indicative of Vitamin A insufficiency (≤22,000 ng/ml). Co-enrolled sibling participants will be first stratified by RBP levels, then siblings within the same stratum will be equally assigned to different arms to provide greater assurance of balanced treatment assignment. Children will be tested for vitamin levels and immune responses before and after influenza virus vaccinations to determine if vitamin supplementation improves the influenza virus vaccine-induced antibody immune response. All participants will receive two doses of an influenza virus vaccination administered at least 28 days apart. Vitamin levels and antibody responses toward the vaccine will be measured on day 0 (baseline levels obtained where day 0 equals the first influenza virus vaccination administration), day 28, and day 56. Placebo or Vitamins A + D (at the levels of 20,000 IU and 2,000 IU, respectively) will be administered orally on the days of vaccination. Blood serum samples will be collected from participants on Day 0, prior to receiving influenza virus vaccine on Day 28, and during their Day 56 follow-up visit. Parents will be asked to fill out diary cards to indicate food intake for children during the study period along with an optional food frequency questionnaire given on day 56. Specific measurements on days 28, and 56 will include analyses of vaccine-specific and total IgA, IgG, and IgA/IgG plus IgA/IgM ratios in sera. Functional activities of antibodies toward influenza vaccine will also be measured.
Interventions
BIOLOGICALInfluenza virus vaccine
Children will have the first influenza virus vaccine dose (dose 1) administered on day 0 of the trial, and the second dose (dose 2) administered 28 days later.
DIETARY_SUPPLEMENTVitamins A and D
The chewable gummy contains either Vitamin A (20,000 International Units) and Vitamin D3 (2,000 International Units), which should be fully chewed under supervision of study staff with documentation in the participant's research record and eMAR (electronic medical administration record). The chewable gummy should be administered prior to receiving influenza virus vaccination.
OTHERPlacebo
The chewable gummy matched placebo will be formulated with gelatin base and tangerine oil and match the Vitamin A and D in shape, taste, texture, and appearance. Gummies should be fully chewed under supervision of study staff with documentation in the participant's research record and eMAR (electronic medical administration record). The chewable gummy should be administered prior to receiving influenza virus vaccination.
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 8 Years
Healthy volunteers
Yes
Inclusion criteria
* Resident of the Memphis area community. * Parent or legal guardian willing and able to give informed consent and comply with study requirements.
Exclusion criteria
* Current use of investigational or immunosuppressive drugs (e.g., steroids) at the time of enrollment. * Currently taking a daily (routine) vitamin A, D, or multivitamin. Note: participants who report occasional or sporadic vitamin use will be allowed to enroll. * History of lung disease, asthma, immunodeficiency, sickle cell disease, or any other serious underlying condition or disease in the opinion of the principal investigator. * Evidence of developmental delay or evolving neurological disorders at screening. Current use of antibiotics or antivirals at enrollment. * History of having a severe allergy to eggs or to any inactive ingredient in the influenza virus vaccine * History of a life-threatening reaction to influenza vaccinations * Currently wheezing at the time of enrollment * History of heart, kidney, or lung conditions * History of diabetes * Use of an anti-influenza medication (including amantadine, rimantadine, oseltamivir, and zanamivir) within 14 days prior to enrollment * Acute febrile \[\>100.0°F (37.8°C) oral\] illness or acute respiratory illness (e.g., cough or sore throat) within 3 days prior to enrollment * Previous receipt of current seasonal influenza vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | Day 56 after vaccination | The percentage of 2X increases or conversion from undetectable to detectable response in virus-specific antibody toward any vaccine component after 2 immunizations in intervention and control groups will be reported. |
| Isotype Ratios on Day 56 | Day 56 after vaccination | Isotype ratios will be summarized with descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | Day 56 after vaccination | Secondary analyses will examine sero-conversion based on antibody functions (HAI or neutralization) defined as antibody titers of \<1:40 converting to ≥1:40, or a four-fold increase in titer for participants with a starting titer of ≥1:40. Sero-conversion rate (expressed as percentage) will be estimated with 95% confidence interval. The rate difference will be described with point estimate and 95% confidence interval. |
| Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | Day 56 after vaccination | Secondary analyses will examine sero-conversion based on antibody functions (HAI or neutralization) defined as antibody titers of \<1:40 converting to ≥1:40, or a four-fold increase in titer for participants with a starting titer of ≥1:40. Sero-conversion rate (expressed as percentage) will be estimated with 95% confidence interval for participants sufficient and insufficient in vitamin A at screening. |
| HAI Titers at Day 56 After Vaccination, Overall | Day 56 after vaccination | — |
| HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | Day 56 after vaccination | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A&D-S1 Participants receiving influenza virus vaccine plus vitamin A and D supplements in 2015-16 season | 5 |
| Placebo - S1 Participants receiving influenza virus vaccine plus matched placebo in 2015-16 season | 4 |
| A&D - S2 Participants receiving influenza virus vaccine plus vitamin A and D supplements in 2016-17 season | 22 |
| Placebo - S2 Participants receiving influenza virus vaccine plus matched placebo in 2016-17 season | 22 |
| A&D - S3 Participants receiving influenza virus vaccine plus vitamin A and D supplements in 2017-18 season | 12 |
| Placebo - S3 Participants receiving influenza virus vaccine plus matched placebo in 2017-18 season | 14 |
| Total | 79 |
Baseline characteristics
| Characteristic | A&D-S1 | Placebo - S1 | A&D - S2 | Placebo - S2 | A&D - S3 | Placebo - S3 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 4 Participants | 22 Participants | 22 Participants | 12 Participants | 14 Participants | 79 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 7 years | 3.5 years | 5 years | 4 years | 3 years | 5 years | 5 years |
| Ethnicity (NIH/OMB) Ethnicity Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Ethnicity Not Hispanic or Latino | 5 Participants | 4 Participants | 21 Participants | 22 Participants | 12 Participants | 14 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Ethnicity Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black | 5 Participants | 4 Participants | 15 Participants | 16 Participants | 8 Participants | 9 Participants | 57 Participants |
| Race/Ethnicity, Customized Race White | 0 Participants | 0 Participants | 7 Participants | 6 Participants | 4 Participants | 5 Participants | 22 Participants |
| Region of Enrollment United States | 5 Participants | 4 Participants | 22 Participants | 22 Participants | 12 Participants | 14 Participants | 79 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 14 Participants | 14 Participants | 6 Participants | 6 Participants | 46 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 8 Participants | 8 Participants | 6 Participants | 8 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 22 | 0 / 22 | 0 / 12 | 0 / 14 |
| other Total, other adverse events | 5 / 5 | 2 / 4 | 6 / 22 | 6 / 22 | 4 / 12 | 3 / 14 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 | 0 / 22 | 0 / 22 | 0 / 12 | 0 / 14 |
Outcome results
Primary
Isotype Ratios on Day 56
Isotype ratios will be summarized with descriptive statistics.
Time frame: Day 56 after vaccination
Population: Subjects with complete isotype data at day 56. Subjects with an undetermined assay result were not included in analyses. In some cases, the limit of detection (LOD) for the assay was reached and that LOD value was used in calculations.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| A&D - S1 | Isotype Ratios on Day 56 | IgA/IgM | 2.48 ratio |
| A&D - S1 | Isotype Ratios on Day 56 | IgA/IgG1 | 0.4 ratio |
| A&D - S1 | Isotype Ratios on Day 56 | IgA/IgG2 | 0.71 ratio |
| A&D - S1 | Isotype Ratios on Day 56 | IgA/IgG3 | 2.73 ratio |
| Placebo - S1 | Isotype Ratios on Day 56 | IgA/IgM | 1.37 ratio |
| Placebo - S1 | Isotype Ratios on Day 56 | IgA/IgG2 | 0.69 ratio |
| Placebo - S1 | Isotype Ratios on Day 56 | IgA/IgG1 | 0.3 ratio |
| Placebo - S1 | Isotype Ratios on Day 56 | IgA/IgG3 | 3.03 ratio |
| A&D - S2 | Isotype Ratios on Day 56 | IgA/IgG1 | 0.3 ratio |
| A&D - S2 | Isotype Ratios on Day 56 | IgA/IgM | 1.21 ratio |
| A&D - S2 | Isotype Ratios on Day 56 | IgA/IgG3 | 1.44 ratio |
| A&D - S2 | Isotype Ratios on Day 56 | IgA/IgG2 | 0.96 ratio |
| Placebo - S2 | Isotype Ratios on Day 56 | IgA/IgG1 | 0.27 ratio |
| Placebo - S2 | Isotype Ratios on Day 56 | IgA/IgM | 1.21 ratio |
| Placebo - S2 | Isotype Ratios on Day 56 | IgA/IgG3 | 1.68 ratio |
| Placebo - S2 | Isotype Ratios on Day 56 | IgA/IgG2 | 1.13 ratio |
| A&D - S3 | Isotype Ratios on Day 56 | IgA/IgG3 | 2.4 ratio |
| A&D - S3 | Isotype Ratios on Day 56 | IgA/IgM | 0.86 ratio |
| A&D - S3 | Isotype Ratios on Day 56 | IgA/IgG2 | 0.65 ratio |
| A&D - S3 | Isotype Ratios on Day 56 | IgA/IgG1 | 0.21 ratio |
| Placebo - S3 | Isotype Ratios on Day 56 | IgA/IgG1 | 0.28 ratio |
| Placebo - S3 | Isotype Ratios on Day 56 | IgA/IgM | 1 ratio |
| Placebo - S3 | Isotype Ratios on Day 56 | IgA/IgG2 | 0.75 ratio |
| Placebo - S3 | Isotype Ratios on Day 56 | IgA/IgG3 | 3.02 ratio |
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG1 at day 56 in 2015-16 seasonp-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG1 at day 56 in 2016-17 seasonp-value: 0.49Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG1 at day 56 in 2017-18 seasonp-value: 0.5Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG2 at day 56 in 2015-16 seasonp-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG2 at day 56 in 2016-17 seasonp-value: 0.76Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG2 at day 56 in 2017-18 seasonp-value: 0.65Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG3 at day 56 in 2015-16 seasonp-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG3 at day 56 in 2016-17 seasonp-value: 0.76Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgG3 at day 56 in 2017-18 seasonp-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgM at day 56 in 2015-16 seasonp-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgM at day 56 in 2016-17 seasonp-value: 0.95Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis: No difference between intervention and placebo groups in the ratio of IgA/IgM at day 56 in 2017-18 seasonp-value: 0.34Wilcoxon (Mann-Whitney)
Primary
Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera
The percentage of 2X increases or conversion from undetectable to detectable response in virus-specific antibody toward any vaccine component after 2 immunizations in intervention and control groups will be reported.
Time frame: Day 56 after vaccination
Population: All enrolled subjects who satisfied the inclusion/exclusion criteria were included in the analysis. For the four participants who didn't complete the study, results after one immunization were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A&D - S1 | Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | 80 percentage of participants |
| Placebo - S1 | Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | 75 percentage of participants |
| A&D - S2 | Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | 100 percentage of participants |
| Placebo - S2 | Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | 100 percentage of participants |
| A&D - S3 | Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | 100 percentage of participants |
| Placebo - S3 | Percentage of Participants With Positive Responses in Virus-specific Antibody in Sera | 100 percentage of participants |
Secondary
HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening
Time frame: Day 56 after vaccination
Population: Subjects with complete HAI data at day 56. Subjects without a day 56 sample were not included in analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| A&D - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 5 titers |
| A&D - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 42.5 titers |
| A&D - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 200 titers |
| A&D - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 720 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 5 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 640 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 1810 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 40 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 640 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 1280 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 80 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 80 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 2560 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 1280 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 80 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 320 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 640 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| A&D-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 5 titers |
| A&D-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 320 titers |
| A&D-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| A&D-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| Placebo-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 5 titers |
| Placebo-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| Placebo-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 480 titers |
| Placebo-S1 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| A&D-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 640 titers |
| A&D-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 1545 titers |
| A&D-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| A&D-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| Placebo-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 640 titers |
| Placebo-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| Placebo-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 640 titers |
| Placebo-S2 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 5 titers |
| A&D-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
| A&D-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 640 titers |
| A&D-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 400 titers |
| A&D-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 42.5 titers |
| Placebo-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 42.5 titers |
| Placebo-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 1920 titers |
| Placebo-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 1920 titers |
| Placebo-S3 Non-VAS | HAI Titers at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 5 titers |
Secondary
HAI Titers at Day 56 After Vaccination, Overall
Time frame: Day 56 after vaccination
Population: Subjects with complete HAI data at day 56. Subjects without a day 56 sample were not included in analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| A&D - S1 | HAI Titers at Day 56 After Vaccination, Overall | B/Brisbane | 5 titers |
| A&D - S1 | HAI Titers at Day 56 After Vaccination, Overall | H3N2 | 320 titers |
| A&D - S1 | HAI Titers at Day 56 After Vaccination, Overall | H1N1 | 5 titers |
| A&D - S1 | HAI Titers at Day 56 After Vaccination, Overall | B/Phuket | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, Overall | B/Phuket | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, Overall | H1N1 | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, Overall | B/Brisbane | 5 titers |
| Placebo - S1 | HAI Titers at Day 56 After Vaccination, Overall | H3N2 | 480 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, Overall | B/Brisbane | 5 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, Overall | H1N1 | 640 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, Overall | H3N2 | 1810 titers |
| A&D - S2 | HAI Titers at Day 56 After Vaccination, Overall | B/Phuket | 5 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, Overall | B/Phuket | 40 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, Overall | H3N2 | 1093 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, Overall | B/Brisbane | 40 titers |
| Placebo - S2 | HAI Titers at Day 56 After Vaccination, Overall | H1N1 | 640 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, Overall | H3N2 | 640 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, Overall | H1N1 | 905 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, Overall | B/Phuket | 5 titers |
| A&D - S3 | HAI Titers at Day 56 After Vaccination, Overall | B/Brisbane | 5 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, Overall | H3N2 | 960 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, Overall | H1N1 | 1280 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, Overall | B/Brisbane | 42.5 titers |
| Placebo - S3 | HAI Titers at Day 56 After Vaccination, Overall | B/Phuket | 5 titers |
Secondary
Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening
Secondary analyses will examine sero-conversion based on antibody functions (HAI or neutralization) defined as antibody titers of \<1:40 converting to ≥1:40, or a four-fold increase in titer for participants with a starting titer of ≥1:40. Sero-conversion rate (expressed as percentage) will be estimated with 95% confidence interval for participants sufficient and insufficient in vitamin A at screening.
Time frame: Day 56 after vaccination
Population: Subjects with complete HAI data at day 56. Subjects without a day 56 sample were not included in analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 0 percentage of participants |
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 0 percentage of participants |
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 0 percentage of participants |
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 100 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 0 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 81.8 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 72.7 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 45.5 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 36.4 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 100 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 63.6 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 90.9 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 72.7 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 71.4 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 42.9 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 42.9 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 100 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 87.5 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 37.5 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 50.0 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 25.0 percentage of participants |
| A&D-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 0 percentage of participants |
| A&D-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 0 percentage of participants |
| A&D-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 66.7 percentage of participants |
| A&D-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 0 percentage of participants |
| Placebo-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 0 percentage of participants |
| Placebo-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 0 percentage of participants |
| Placebo-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 0 percentage of participants |
| Placebo-S1 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 0 percentage of participants |
| A&D-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 10.0 percentage of participants |
| A&D-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 20.0 percentage of participants |
| A&D-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 70.0 percentage of participants |
| A&D-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 60.0 percentage of participants |
| Placebo-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 88.9 percentage of participants |
| Placebo-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 33.3 percentage of participants |
| Placebo-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 66.7 percentage of participants |
| Placebo-S2 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 44.4 percentage of participants |
| A&D-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 75.0 percentage of participants |
| A&D-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 50.0 percentage of participants |
| A&D-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 25.0 percentage of participants |
| A&D-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 0.0 percentage of participants |
| Placebo-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H1N1 | 83.3 percentage of participants |
| Placebo-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Phuket | 33.3 percentage of participants |
| Placebo-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | H3N2 | 66.7 percentage of participants |
| Placebo-S3 Non-VAS | Percentage of Participants With Seroconversion at Day 56 After Vaccination, by Vitamin A Levels at Screening | B/Brisbane | 16.7 percentage of participants |
Secondary
Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall
Secondary analyses will examine sero-conversion based on antibody functions (HAI or neutralization) defined as antibody titers of \<1:40 converting to ≥1:40, or a four-fold increase in titer for participants with a starting titer of ≥1:40. Sero-conversion rate (expressed as percentage) will be estimated with 95% confidence interval. The rate difference will be described with point estimate and 95% confidence interval.
Time frame: Day 56 after vaccination
Population: Subjects with complete HAI data at day 56. Subjects without a day 56 sample were not included in analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H1N1 | 0 percentage of participants |
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H3N2 | 40.0 percentage of participants |
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Phuket | 0 percentage of participants |
| A&D - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Brisbane | 0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Phuket | 0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H3N2 | 50.0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H1N1 | 0 percentage of participants |
| Placebo - S1 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Brisbane | 0 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Brisbane | 28.6 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Phuket | 28.6 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H3N2 | 71.4 percentage of participants |
| A&D - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H1N1 | 71.4 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H1N1 | 95.0 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Brisbane | 55.0 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H3N2 | 80.0 percentage of participants |
| Placebo - S2 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Phuket | 55.0 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Phuket | 45.5 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Brisbane | 27.3 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H3N2 | 72.7 percentage of participants |
| A&D - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H1N1 | 72.7 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H3N2 | 50.0 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Phuket | 28.6 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | B/Brisbane | 35.7 percentage of participants |
| Placebo - S3 | Percentage of Participants With Seroconversion at Day 56 After Vaccination, Overall | H1N1 | 85.7 percentage of participants |
Comparison: H1N195% CI: [0, 0]
Comparison: H1N195% CI: [-51.7, 6.2]
Comparison: H1N195% CI: [-49.4, 26.5]
Comparison: H3N295% CI: [-70.1, 56.1]
Comparison: H3N295% CI: [-38.8, 20.6]
Comparison: H3N295% CI: [-17.5, 57.9]
Comparison: B/Phuket95% CI: [0, 0]
Comparison: B/Phuket95% CI: [-54.1, 5.8]
Comparison: B/Phuket95% CI: [-23.1, 53.3]
Comparison: B/Brisbane95% CI: [0, 0]
Comparison: B/Brisbane95% CI: [-54.1, 5.8]
Comparison: B/Brisbane95% CI: [-45.4, 30.5]