ETEC

ETEC causes diarrhea in children and tourists

Enterotoxigenic Escherichia coli (ETEC) are one of the most important causes of diarrhea in young children in low and middle-income countries (LMIC) as well as in travelers to these countries. Being responsible for tens of thousands of child deaths in LMIC these bacteria can inflict a nutritional insult in many many more. The secreted heat-stable (ST) and heat-labile (LT) enterotoxins elicit net secretion of salts and water, resulting in diarrhea, in the most serious cases producing a profuse cholera-like condition.

Controlled human infection model

At the Department of Clinical Science, UiB and Haukeland University Hospital, our efforts have centered on developing a human challenge model with an ST-only ETEC strain and immunological assays to evaluate human immune responses to ETEC infection and future ETEC vaccine candidates. The model will be used to test protective efficacy of ST-based vaccine candidates; in other words whether volunteers who have been given the vaccine candidate are less affected than those given a placebo vaccine when they are later experimentally infected with an ETEC strain.

Until now, 60 volunteers have been experimentally infected with three different epidemiologically relevant ETEC strains. The project has attracted attention from local media and TV. Our project have shown the feasibility of conducting human challenge studies in Bergen, and an ETEC strain to test ST-based vaccine components has been identified. The ETEC strain TW11681 was tested in 9 of these volunteers and found to elicit abdominal symptoms in some volunteers, but hardly any diarrheal disease. However, the TW10722 strains was found to be SAFE and suitable as it could cause diarrheal illness in 79% of adult volunteers.

Immune responses against ETEC

Immunoassays to evaluate responses towards major ETEC antigens are being developed. The proliferation of ETEC during infection, and sublingual saliva as a noninvasive proxy for intestinal immune induction has been assessed. Further studies on immune responses include mass cytometry (CyTOF) examination of peripheral blood immune cell subsets during infection, and multiplex bead-based assays that measure antibody responses to major ETEC virulence factors.

Cross-faculty and international collaboration

The ETEC research work performed in Bergen involves researchers at the University of Bergen, including from the Faculty of Medicine and the Faculty of Mathematics and Natural Sciences, from Haukeland University Hospital, and from NORCE Norwegian Research Centre AS. More information regarding the vaccine development arm of the project can be found here.

The research is done in collaboration with researchers at Norwegian Institute of Public Health in Oslo, the University of Maryland School of Medicine in Baltimore, University of Virginia in Charlottesville, Tulane University in New Orleans, Kansas State University in Manhattan, Indian Institute of Science in Bangalore and Institut Pasteur in Paris.

Funding

The ETEC research group has been made possible by grants from the Research Council of Norway, the European Union (through the STOPENTERICS network), EVI and PATH.