Vitamin A (VA) alone or combined with retinoic acid (VARA) in the neonatal period improves the secondary response to tetanus toxoid (TT) in VA‐deficient rats

We have tested whether giving VA early in life can improve the antibody response to later immunization. Using a rat model, we compared 3 treatments given to neonates (d‐6‐8) on the anti‐TT primary (1°) IgG response at 3 wk of age, and the secondary (2°) anti‐TT IgG as well as the 1° IgG response to a novel TD antigen (KLH) given at 8 wk. Neonates were given either oil (control); VA alone; retinoic acid (RA); or VA & RA (10:1, VARA); 1d before, with, and 1d after TT immunization. At 3 wk of age, the 1° anti‐TT IgG response was determined and rats were then weaned onto either VA‐deficient (VAD) or VA‐sufficient (VAS) diet. Results: Anti‐TT 1° IgG in controls was 41–67% lower compared to the other 3 groups, though non‐significant. At 9 wk, in VAD rats, anti‐TT 2° IgG in VA and VARA groups were 6‐ & 5‐fold > control (P ≤ 0.05). Anti‐KLH 1° IgG in VA and VARA groups were 8‐ & 5‐fold > control and RA, respectively (P ≤ 0.05). Plasma and liver retinol determinations confirmed that neonatal supplementation with VA or VARA maintained concentrations above critical levels, while it was not a factor in rats fed VAS diet post‐weaning. Conclusions: VA and VARA given in the neonatal period increased the later life recall response of VAD rats to TT, as well as improved their 1° response to a novel antigen. When neonatal VA supplementation prevents the onset of VA deficiency, the benefit on the antibody response is evident at a later age. (Support: DK41479)