Influenza Virus Vaccine Plus Vitamin A and D Supplements for Prevention of Respiratory Virus Infections in Children

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.

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