Human Mucosal IgA Immune Responses against Enterotoxigenic Escherichia coli

Infection with enterotoxigenic Escherichia coli (ETEC) is a major contributor to diarrheal illness in children in low- and middle-income countries and travelers to these areas. There is an ongoing effort to develop vaccines against ETEC, and the most reliable immune correlate of protection against ETEC is considered to be the small intestinal secretory IgA response that targets ETEC-specific virulence factors. Since isolating IgA from small intestinal mucosa is technically and ethically challenging, requiring the use of invasive medical procedures, several other indirect methods are used as a proxy for gauging the small intestinal IgA responses. In this review, we summarize the literature reporting on anti-ETEC human IgA responses observed in blood, activated lymphocyte assayss, intestinal lavage/duodenal aspirates, and saliva from human volunteers being experimentally infected with ETEC. We describe the IgA response kinetics and responder ratios against classical and noncanonical ETEC antigens in the different sample types and discuss the implications that the results may have on vaccine development and testing.