Effect of vitamin A supplementation on immunoglobulin G subclass responses to tetanus toxoid in children.

Previously, we demonstrated that administering vitamin A supplements to children resulted in a significant increase in the immunoglobulin G (IgG) response generated against a vaccine dose of tetanus toxoid (TT) (R. D. Semba et al., J. Nutr. 122:101-107, 1991). However, from these analyses we could not determine whether there was an increase in levels of IgG of the subclass presumed to be important for protection against challenge by the toxin or whether there was simply a general increase in the levels of all the IgG subclasses expressing anti-TT activity. The goal of this study was to determine the profile of the anti-TT IgG subclasses in children receiving vitamin A supplementation or a placebo in order to assess the potential utility of the enhanced anti-TT response. In a randomized, double-masked, placebo-controlled clinical trial, the levels of the different anti-TT IgG subclasses were measured in 139 Indonesian preschool children (3 to 6 years of age) 2 weeks before and 3 weeks after immunization. Baseline anti-TT levels and immunization histories were used to separate those children who were responding to TT for the first time from those who responded in a secondary fashion because of previous exposure to TT. Children who were given vitamin A prior to immunization had significant increases in IgG1 levels regardless of whether they were undergoing primary or memory reactions. In the group of individuals who underwent a secondary response to TT, vitamin A supplementation was also associated with a modest but significant change in the levels of anti-TT IgG3. There were only minor changes in the levels of anti-TT IgG2 and IgG4. Since IgG1 is the subclass associated with a protective response to TT immunization, these results suggest that vitamin A supplementation may be a safe and effective intervention to enhance the relevant humoral response to TT and other vaccine antigens.