Vitamin A supplementation and retinoic acid treatment in the regulation of antibody responses in vivo.

Vitamin A (VA, retinol) is essential for normal immune system maturation, but the effect of VA(1) on antibody production, the hallmark of successful vaccination, is still not well understood. In countries where VA deficiency is a public health problem, many children worldwide are now receiving VA along with immunizations against poliovirus, measles, diphtheria, pertussis, and tetanus. The primary goal has been to provide enough VA to protect against the development of VA deficiency for a period of 4-6 months. However, it is also possible that VA might promote the vaccine antibody response. Several community studies, generally of small size, have been conducted in children supplemented with VA at the time of immunization, as promoted by the World Health Organization/UNICEF. However, only a few studies have reported differences in antibody titers or seroconversion rates due to VA. However, VA status was not directly assessed, and in some communities children were often breast fed, another strategy for preventing VA deficiency. Some of the vaccines used induced a high rate of seroconversion, even without VA. In children likely to have been VA deficient, oral polio vaccine seroconversion rate was increased by VA. In animal models, where VA status was controlled and VA deficiency confirmed, the antibody response to T-cell-dependent (TD) and polysaccharide antigens was significantly reduced, congruent with other defects in innate and adaptive immunity. Moreover, the active metabolite of VA, retinoic acid (RA) can potentiate antibody production to TD antigens in normal adult and neonatal animals. We speculate that numerous animal studies have correctly identified VA deficiency as a risk factor for low antibody production. A lack of effect of VA in human studies could be due to a low rate of VA deficiency in the populations studied or low sample numbers. The ability to detect differences in antibody response may also depend on the vaccine-adjuvant combination used. Future studies of VA supplementation and immunization should include assessment of VA status and a sufficiently large sample size. It would also be worthwhile to test the effect of neonatal VA supplementation on the response to immunization given after 6 months to 1 year of age, as VA supplementation, by preventing the onset of VA deficiency, may improve the response to immunizations given later on.