Enterotoxigenic Escherichia coli (ETEC)
Enterotoxigenic Escherichia coli (ETEC) is a group of E. coli that constitutes the leading bacterial cause of diarrhea among international travelers and children in developing nations. Infection can lead to severe dehydration and, for the service members deployed to less developed countries, decreased readiness.
A team of researchers at the Naval Medical Research Center (NMRC) is spearheading the development of an ETEC vaccine. One promising avenue of exploration is an adhesin-based vaccine approach.
ETEC bacteria attach to the intestinal lining via proteins perched at the tips of surface hair-like structures called fimbriae. The research team is attempting to generate antibodies against these tip proteins, which normally dock the bacterium to the intestinal surface, preventing ETEC from binding to target cells.
Identifying Vaccine Targets
The NMRC research team is attempting to create a vaccine by focusing on a group of three adhesins that together could confer protection against more than 80 percent of ETEC types that cause moderate to severe illness. The researchers had previously performed groundbreaking research that identified these tip adhesins as viable vaccine candidates. The team has proven that this approach is effective in vitro, and is now focused on in vivo testing.
To create a passive vaccine—in which antibodies are supplied directly to the vaccine recipient—the research team vaccinated cows against ETEC adhesins. The vaccine stimulated the production of antibodies that the cows then passed on to newborn calves via the colostrum in their milk.
The researchers collected the colostrum and processed it to create a powdered product that contains high levels of the adhesin-specific antibodies. The group then showed that this product, given as a drink, protects human volunteers against an experimental ETEC infection. This research has been undertaken in conjunction with Johns Hopkins University and a private industry partner through subawards facilitated by HJF.
Prompting a Protective Response
The researchers are also working on an active vaccine that will contain three to four different tip adhesions and will prompt the body to create its own protective antibodies. The vaccine envisioned as the final product of this effort is expected to have dual use, in that it would not only benefit U.S. service members deploying overseas, but also young children living in developing areas of the world.
This work is partially funded by a grant from the National Institute of Allergy and Infectious Diseases and is being done in collaboration with a research team at the University of Colorado.