Measles immunization remains problematic because of blocking maternal antibodies and other host factors which prevent effective immunization. One potential solution is a safe adjuvant to measles immunization. Vitamin A is known to enhance immunity to measles during natural measles infection and to increase antibody responses to vaccination. Our preliminary studies suggest that vitamin A enhances the antibody response to measles in six- month-old infants, even in infants who have high levels of maternal antibodies to measles. These studies suggest that oral vitamin A supplementation simultaneously with measles immunization is a strategy which can be used to overcome blocking maternal antibodies and allow effective immunization in very young infants. It also appears that infants with a recent history of infection have reduced antibody responses to measles. Other host factors besides blocking maternal antibodies may also contribute to measles vaccine failure. While preliminary studies with vitamin A are encouraging, the potential long-term effect of vitamin A on measles antibody and cell-mediated immunity are unknown.
The specific aims are: (1) to confirm the role of vitamin A as an adjuvant to measles immunization, (2) to characterize long-term changes in cell- mediated immunity after measles immunization with vitamin A, (3) to gain insight into the biological mechanisms by which vitamin A enhances the immune response to measles, (4) to investigate other potential host factors which may cause primary vaccine failure in very young infants.
These aims will be met through two separate, randomized, placebo- controlled clinical trials of vitamin A supplementation with standard titer measles immunization (Schwarz) in over 800 six- and nine-month-old infants in Indonesia. We propose to measure antibody responses to measles using the more sensitive plaque-reduction-neutralization assay, to have longer follow-up of vaccinees, to characterize lymphocyte subsets and proliferation, and to examine effects on in-vitro production of cytokines. If vitamin A is demonstrated to be a safe and effective means of enhancing immunity to measles, there may be practical significance in possible integration of vitamin A with measles immunization programs, and potential significance in using vitamin A as an adjuvant for existing and future measles vaccines.
