Vaccines for enterotoxigenic Escherichia coli:: current status

Purpose of review Enterotoxigenic Escherichia coli (ETEC) remain major causes of infantile diarrhea in the developing world and of travelers' diarrhea in visitors to these areas from industrialized countries, although the relative importance of these pathogens in these settings may be decreasing. The pathogenesis of ETEC infections has been well understood for almost two decades, and there is good evidence for acquired immunity after infection. Nevertheless, currently there is no effective ETEC vaccine. This review evaluates the current status of ETEC vaccine development. Recent findings ETEC organisms express fimbrial (or fibrillar) colonization factor antigens that function as adhesins to promote their attachment to the small intestinal epithelium. They secrete either (or both) of two major protein enterotoxins that induce fluid and electrolyte secretion. Vaccine development during the last decade has targeted the components of the three major colonization factor antigens as well as the immunogenic heat-labile enterotoxin. This strategy was expected to cover 90% of infecting strains, leaving unprotected only those strains without major. colonization factor antigens and those that express only the poorly immunogenic heat-stable enterotoxin. Recent experiences have questioned the validity of the current vaccine strategy since new reports indicate that (1) the number of recognized colonization factor antigens of ETEC has increased to more than 21, (2) epidemiologic field studies of children in endemic areas suggest that infection with ETEC of a given colonization factor antigen/toxin phenotype may not confer protection on reinfection with other strains of the same colonization factor antigen/toxin phenotype, and (3) a major field trial of a heat-killed ETEC vaccine expressing colonization factor antigens and containing the B subunit of cholera toxin as a surrogate for E coli heat-labile enterotoxin was ineffective against ETEC infections that should have been "vaccine preventable." New vaccine strategies have been developed to deliver ETEC antigens to the mucosal immune system. Summary Although new vaccines are being developed to improve immunogenicity over that of the heat-killed vaccine, the current strategy for antigen inclusion has been challenged and new, common antigens may have to be defined to achieve the goal of an effective vaccine against ETEC.