Orally delivered toxin-binding protein protects against diarrhoea in a murine cholera model

The ongoing seventh cholera pandemic, which began in 1961, poses an escalating threat to public health. There is a need for new cholera control measures, particularly ones that can be produced at low cost, for the one billion people living in cholera-endemic regions. Orally delivered V_HHs, functioning as target-binding proteins, have been proposed as a potential approach to control gastrointestinal pathogens. Here, we describe the development of an orally deliverable bivalent V_HH construct that binds to the B-pentamer of cholera toxin, showing that it inhibits toxin activity in a murine challenge model. Infant mice given the bivalent V_HH prior to V. cholerae infection exhibit a significant reduction in cholera toxin-associated intestinal fluid secretion and diarrhoea. In addition, the bivalent V_HH reduces V. cholerae colonization levels in the small intestine by a factor of 10. This cholera toxin-binding protein holds promise for protecting against severe diarrhoea associated with cholera.