Abstract
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.
Highlights
Escherichia coli was discovered in 1919 by the German-Austrian pediatrician Theodor Escherich and named after him [1]
There is currently an effort to produce vaccines based on stable toxin (ST) [78,79], and, if successful, it is likely that a combination of ST and labile toxin (LT) vaccine antigens could protect against the most debilitating diarrheal episodes caused by enterotoxigenic Escherichia coli (ETEC)
Study sizes are usually small; ETEC strains used in the models only represent a small proportion of the ETEC population, and they have usually been selected based on their ability to colonize and cause disease in adults; the studies are conducted in an artificial and controlled setting; the study populations are always healthy adults who often differ with respect to age, race, diet, and nutritional status; different doses are used even when studying the same strain
Summary
Escherichia coli was discovered in 1919 by the German-Austrian pediatrician Theodor Escherich and named after him [1]. ETEC infects orally, and it colonizes the small intestinal mucosa It does not invade the intestinal epithelial cells but secretes enterotoxins that cause diarrhea by activating epithelial cell surface receptors that are normally. ETEC infections and diarrhea are often widespread in low- and middle-income countries (LMICs) It mainly affects young children, but it is a commonly encountered health problem among adult travelers and military personnel deployed to these areas [11,12]. Several promising vaccine targets have been identified, including, mainly, the ETEC colonization factors and toxins, and it is generally believed that a strong, small intestinal mucosal IgA response against these antigens is needed to protect against ETEC [21,22,23]. We summarize and interpret the current knowledge of human IgA immune responses to ETEC infections and suggest ways to increase our understanding of its protective effect in order to guide vaccine design
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