Format

Send to

Choose Destination
Infect Immun. 2019 Jan 24;87(2). pii: e00634-18. doi: 10.1128/IAI.00634-18. Print 2019 Feb.

Establishment, Validation, and Application of a New World Primate Model of Enterotoxigenic Escherichia coli Disease for Vaccine Development.

Author information

1
Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA.
2
Bacteriology Department, Naval Medical Research Unit No. 6, Lima, Peru.
3
Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA michael.g.prouty2.mil@mail.mil.
4
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Abstract

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.

KEYWORDS:

CfaE; enterotoxigenic Escherichia coli ; nonhuman primates; vaccine

PMID:
30510102
PMCID:
PMC6346130
DOI:
10.1128/IAI.00634-18
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center