Overcoming enterotoxigenic Escherichia coli pathogen diversity: Translational molecular approaches to inform vaccine design

Enterotoxigenic Escherichia coli (ETEC) are a genetically diverse E. coli pathovar that share in the ability to produce heat-labile toxin and/or heat-stable toxins. While these pathogens contribute substantially to the burden of diarrheal illness in developing countries, at present, there is no suitable broadly protective vaccine to prevent these common infections. Most vaccine development attempts to date have followed a classical approach involving a relatively small group of antigens. The extraordinary underlying genetic plasticity of E. coli has confounded the antigen valency requirements based on this approach. The recent discovery of additional virulence proteins within this group of pathogens, as well as the availability of whole-genome sequences from hundreds of ETEC strains to facilitate identification of conserved molecules, now permits a reconsideration of the classical approaches, and the exploration of novel antigenic targets to complement existing strategies overcoming antigenic diversity that has impeded progress toward a broadly protective vaccine. Progress to date in antigen discovery and methods currently available to explore novel immunogens are outlined here.