Effects of neonatal Vitamin A supplementation on response to vaccinations in early infancy.

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.