The Controlled Human Infection Model for Enterotoxigenic Escherichia coli

Chad K Porter; Kawsar R Talaat; Sandra D Isidean; Alwine Kardinaal; Subhra Chakraborty; Ramiro L Gutiérrez; David A Sack; A Louis Bourgeois

doi:10.1007/82_2021_242

The Controlled Human Infection Model for Enterotoxigenic Escherichia coli

Curr Top Microbiol Immunol. 2021 Oct 21. doi: 10.1007/82_2021_242. Online ahead of print.

Authors

Chad K Porter¹, Kawsar R Talaat², Sandra D Isidean^{3

4}, Alwine Kardinaal⁵, Subhra Chakraborty⁶, Ramiro L Gutiérrez³, David A Sack⁶, A Louis Bourgeois⁷

Affiliations

¹ Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, 20910, USA. chad.k.porter2.civ@mail.mil.
² Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
³ Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, 20910, USA.
⁴ Henry M. Jackson Foundation, Bethesda, MD, 20817, USA.
⁵ NIZO Food Research, Ede, P.O. Box 20, 6710 BA EDE, Kernhemseweg 2, 6718 ZB EDE, The Netherlands.
⁶ Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
⁷ PATH|Center for Vaccine Innovation and Access, 455 Massachusetts Avenue NW, Suite 1000, Washington, DC, 20001, USA.

PMID: 34669040
DOI: 10.1007/82_2021_242

Abstract

The controlled human infection model (CHIM) for enterotoxigenic Escherichia coli (ETEC) has been instrumental in defining ETEC as a causative agent of acute watery diarrhea, providing insights into disease pathogenesis and resistance to illness, and enabling preliminary efficacy evaluations for numerous products including vaccines, immunoprophylactics, and drugs. Over a dozen strains have been evaluated to date, with a spectrum of clinical signs and symptoms that appear to replicate the clinical illness seen with naturally occurring ETEC. Recent advancements in the ETEC CHIM have enhanced the characterization of clinical, immunological, and microbiological outcomes. It is anticipated that omics-based technologies applied to ETEC CHIMs will continue to broaden our understanding of host-pathogen interactions and facilitate the development of primary and secondary prevention strategies.

Keywords: CHIM; Clinical trial; Controlled human infection model; Diarrhea; Enterotoxigenic Escherichia coli; ETEC; Experimental infection; Travelers’ diarrhea; Vaccine.