Vitamin A Supplementation at Birth Alters Vaccine Immune Responses Without Improving Antibody Levels in Infants

BACKGROUND: Vitamin A (VA) deficiency impairs immune function. STUDY DESIGN: A randomized, placebo-controlled intervention trial, stratified by sex and birthweight median (BWM), was conducted in 306 infants in Dhaka, Bangladesh to evaluate the effect of 50,000 IU VA given within 48 h of birth on responses to Bacillus Calmette Guérin (BCG), oral polio virus (OPV), Tetanus Toxoid (TT) and Hepatitis B virus (HBV) vaccines. METHODS: VA, BCG and OPV were administered within 48 h of birth. OPV was again administered at 6, 10 and 14 w with TT and HBV. Vaccine-specific responses included delayed-type hypersensitivity (DTH) at 15 w for BCG and antibody responses at 15 w (ex vivo PBMC secretion) and 2 y for OPV (IgA, IgG), TT (IgG) and HBV (IgG). T-cell proliferation and cytokine production (IFN-γ, IL-2, -4, -5, -10, -13 and -17A) in response to vaccine antigens and a polyclonal stimulus (staphylococcus enterotoxin B [SEB]) were measured at 6 w, 15 w and 2 y. Statistical analysis determined main effects of the intervention, and interactions with sex and birthweight. RESULTS: VA increased the DTH response in infants above the BWM but did not affect antibody responses to vaccines. The CD4 T-cell stimulation index (SI) was reduced by VA for BCG (6 w) and SEB (overall). VA increased TT- and HBV-specific IL-2 and IL-5 at 15 w and increased SEB-stimulated IL-5 in girls but decreased IL-5 in boys at 15 w. VA increased BCG-specific IL-13 and SEB-stimulated IL-5 in girls. VA decreased TT-specific and SEB-stimulated IL-17 in boys and decreased IL-10 in response to BCG, HBV (below BWM only) and SEB at 15 w. CONCLUSIONS: Neonatal VA modestly improved the DTH response to BCG but had no effect on antibody responses to OPV, TT and HBV. VA affected CD4 T-cell function, at times in a sex-specific manner. TRIAL REGISTRY: This trial is registered at Clinical. TRIALS: gov. Registry numbers are NCT015839720 and NCT02027610.