Diarrhea, as well most of us know, is characterized by frequent, watery bowel motions, most often brought on by ingesting food or water contaminated with harmful bacteria such as Escherischia coli. In the Western world, diarrhea is more often than not a short-lived, acute illness, picked up from ill-prepared food, such as undercooked meat or unwashed vegetables. It is also suffered by approximately 30-50% of travelers to developing countries that are at high risk of enterotoxigenic E. coli (ETEC), which represents a figure of some 30 million people each year suffering from at least one episode of diarrhea during their trip.
Acute diarrhea is easily treated with over-the-counter medicines or by ‘letting nature take its course’. In the developing world however, chronic diarrhea is a major cause of infant death by dehydration attributed to unclean water supplies and inadequate nutrition. In low and middle income countries, some 300,000 children each year die from this entirely preventable illness.
Currently, there is no vaccine for ETEC-related diarrhea that is suitable to be administered to children, or for international travelers. However, thanks to research at the University of Gothenburg Research Institute (GUVAX) in Sweden, an oral vaccination could be on its way.
In a placebo-controlled phase I study, GUVAX researchers investigated the safety and immunogenicity of an E. coli vaccine that contained four inactivated strains of E. coli, as well as part of a protein from the ETEC type. Human participants were assigned to one of four experimental groups and received two doses of either: the vaccine alone, the vaccine and a high dose adjuvant, the vaccine and a low dose adjuvant, or the placebo. The study was a four-armed, double blinded trial, which means that volunteers did not know which combination of treatments or placebos they would receive.
The trial participants were monitored for any adverse reactions to the vaccine and their antibody responses in fecal samples and blood. Results showed that the vaccine is indeed safe; only a few participants experienced adverse events, and these were mild and non-serious. Moreover, there was no significant difference in the number of adverse events experienced by participants who took the vaccine compared to those who took the placebo, so it cannot be concluded that the adverse reactions were associated directly with the vaccine.
Importantly, the vaccine was shown to be effective. Researchers had hoped that 50% of participants would respond well to the 5 primary vaccine components, when in fact, 75% of participants did so – a much better result than expected.
What happens next?
The promising findings from this study mean that further work to test and develop the vaccine will now go ahead. The University of Gothenburg is planning further clinical studies to investigate how well the vaccine prevents ETEC-related diarrhea in adult travelers to high-risk countries, and to test the safety and immunogenicity of the vaccine in children living in ETEC-endemic areas.