title: Analysis of strategies to successfully vaccinate infants in developing countries against enterotoxigenic E. coli (ETEC) disease.
abstract: Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of diarrhoea in the world, annually affecting up to 400,000,000 children under 5 years of age living in developing countries (DCs). Although ETEC possesses numerous antigens, the relatively conserved colonization factor (CF) antigens and the heat labile enterotoxin (LT) have been associated with protection and most vaccine candidates have exploited these antigens. A safe and effective vaccine against ETEC is a feasible goal as supported by the acquisition of protective immunity. The success of an ETEC vaccine targeting infants and children in DCs will depend on a combination of maximally antigenic vaccine preparations and regimens for their delivery which will produce optimal immune responses to these antigens. Vaccine candidates having a high priority for accelerated development and clinical testing for eventual use in infants would include inactivated ETEC or Shigella hybrids expressing ETEC antigens as well as attenuated ETEC strains which express the major CF antigens and LT toxin B-subunit, as well as attenuated Shigella, Vibrio cholerae and Salmonella typhi hybrids engineered to deliver antigens of ETEC. Candidates for an ETEC vaccine would have to meet the minimal requirement of providing at least 50% protection against severe disease in DCs during the first 2 years of life. The critical roadblock to achieving this goal has not been the science as much as the lack of a sufficiently funded and focused effort to bring it to realization. However, a Product Development Partnership to overcome this hurdle could accelerate the time lines towards when control of ETEC disease in DCs is substantially closer.
authors.affiliation: Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20851-1448, USA. walkerri@cber.fda.gov
authors.forename: Richard I
authors.initials: RI
authors.lastname: Walker
authors.forename: Duncan
authors.initials: D
authors.lastname: Steele
authors.forename: Teresa
authors.initials: T
authors.lastname: Aguado
mesh_terms: D018830:Adhesins, Escherichia coli / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D003906:Developing Countries; D004768:Enterotoxins / Q000276:immunology; D004927:Escherichia coli Infections / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000276:immunology; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D018830:Adhesins, Escherichia coli; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli