Establishment, Validation, and Application of a New World Primate Model of Enterotoxigenic Escherichia coli Disease for Vaccine Development.
The establishment of an animal model that closely approximates enterotoxigenic Escherichia coli (ETEC) disease in humans is critical for the development and evaluation of vaccines against this enteropathogen. Here, we evaluated the susceptibility of Aotus nancymaae, a New World monkey species, to ETEC infection. Animals were challenged orogastrically with 109 to 1011 CFU of the human pathogenic CFA/I+ ETEC strain H10407 and examined for evidence of diarrhea and fecal shedding of bacteria. A clear dose-range effect was obtained, with diarrheal attack rates of 40% to 80%, validated in a follow-on study demonstrating an attack rate of 80% with 1011 CFU of H10407 ETEC. To determine whether this model is an effective approach for assessing ETEC vaccine candidates, we used it to evaluate the ability of the donor strand-complemented CFA/I adhesin CfaE (dscCfaE) to protect against H10407 challenge. In a series of experiments, animals were intranasally vaccinated with dscCfaE alone, dscCfaE with either cholera toxin B-subunit (CTB) or heat-labile toxin (LTB), or phosphate-buffered saline (PBS) alone and then challenged with 1011 CFU of H10407. Control animals vaccinated with PBS had attack rates of 70 to 90% on challenge. Vaccination with dscCfaE, or dscCfaE admixed with CTB or LTB, resulted in a reduction of attack rates, with vaccine efficacies of 66.7% (P = 0.02), 77.7% (P = 0.006), and 42.9% (P = 0.370) to 83.3% (P = 0.041), respectively. In conclusion, we have shown the H10407 ETEC challenge of A. nancymaae to be an effective, reproducible model of ETEC disease, and importantly, we have demonstrated that in this model, vaccination with the prototype vaccine candidate dscCfaE is protective against CF-homologous disease.
['Rollenhagen|Julianne E|JE|', 'Jones|Franca|F|', 'Hall|Eric|E|', 'Maves|Ryan|R|', 'Nunez|Gladys|G|', 'Espinoza|Nereyda|N|', "O'Dowd|Aisling|A|", 'Prouty|Michael G|MG|', 'Savarino|Stephen J|SJ|']
D000281:Administration, Intranasal D000818:Animals D000907:Antibodies, Bacterial D003967:Diarrhea D004195:Disease Models, Animal D054307:Enterotoxigenic Escherichia coli D004927:Escherichia coli Infections D022361:Escherichia coli Vaccines D005243:Feces D006801:Humans D007074:Immunoglobulin G D011323:Primates
enterotoxigenic Escherichia coli vaccine CfaE nonhuman primates