Vaccine Design pp 363-383 | Cite as

Overcoming Enterotoxigenic Escherichia coli Pathogen Diversity: Translational Molecular Approaches to Inform Vaccine Design

  • James M. FleckensteinEmail author
  • David A. Rasko
Part of the Methods in Molecular Biology book series (MIMB, volume 1403)


Enterotoxigenic Escherichia coli (ETEC) are a genetically diverse E. colipathovar 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.

Key words

Escherichia coli Enterotoxigenic Subunit vaccines Bacterial genome Antigenic diversity 



The work described was supported by Grant Number 2R01AI089894 from the National Institute of Allergy and Infectious Diseases (NIAID), the PATH Enteric Vaccine Initiative (EVI), the Bill and Melinda Gates Foundation (OPP1099494), and the Department of Veterans Affairs. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies.


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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Department of MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Molecular Microbiology and Molecular Pathogenesis Program, Division of Biology and Biomedical SciencesWashington University School of MedicineSt. LouisUSA
  3. 3.Medicine Service, Veterans Affairs Medical CenterSt. LouisUSA
  4. 4.Department of Microbiology and Immunology, Institute for Genome SciencesUniversity of Maryland School of MedicineBaltimoreUSA

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