Indirect measurement of intestinal immune responses to an orally administered attenuated bacterial vaccine

Intestinal fluid, saliva, circulating peripheral blood lymphocytes (PBL), and serum samples obtained from 81 human adult subjects who had been orally vaccinated with either Salmonella typhi Ty21a or one of its recombinant derivatives were examined to determine the value of indirect measurements of an antigen-specific intestinal-immunoglobulin A (IgA) response. Salivary IgA failed to provide consistent or correlative responses, and no evidence of a significant relationship was apparent with the intestinal-IgA responses. No significant correlation between the specific increase in responses in serum IgA and intestinal IgA was evident. While the magnitude of the serum IgG response significantly correlated with the intestinal-IgA response (P = 0.00064), it failed to detect 14.8% of the intestinal-IgA responses. The observation that 16.6% of the subjects had delayed serum IgA responses, with a peak occurring after day 23 compared with days 12 to 14, may have contributed to the inadequacy of the serum IgA response as a correlative indicator. The serum IgG responses in these subjects were also of a diminished magnitude. Specific IgA production by circulating PBL was found to be the most sensitive (92.6% response rate) and correlative (P = 0.00071) indicator of a specific intestinal-IgA immune response. However, its value in predicting protective efficacy is untried. These studies confirm that for the assessment of an enteric bacterial vaccine, determination of in vitro specific IgA production by circulating PBL may offer a single measurement of specific immunity which is as useful as serum and intestinal measurements combined.