title: Overcoming Enterotoxigenic Escherichia coli Pathogen Diversity: Translational Molecular Approaches to Inform Vaccine Design.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Campus Box 8051, 660 South Euclid Avenue, St. Louis, MO, USA. jflecken@wustl.edu.|Molecular Microbiology and Molecular Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA. jflecken@wustl.edu.|Medicine Service, Veterans Affairs Medical Center, St. Louis, MO, USA. jflecken@wustl.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Fleckenstein
authors.affiliation: Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism; D054307:Enterotoxigenic Escherichia coli / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control; D022361:Escherichia coli Vaccines / Q000276:immunology*; D006801:Humans; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022361:Escherichia coli Vaccines; D037521:Virulence Factors
keywords: Antigenic diversity; Bacterial genome; Enterotoxigenic; Escherichia coli; Subunit vaccines