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

Marcus Petersson, Franz G. Zingl, Everardo Rodriguez-Rodriguez, Jakob K. H. Rendsvig, Heidi Heinsøe, Emma Wenzel Arendrup, Natalia Mojica, Dario Segura Peña, Nikolina Sekulić, Ute Krengel, Monica L. Fernández-Quintero, Timothy P. Jenkins, Lone Gram, Matthew K. Waldor, Andreas H. Laustsen () and Sandra Wingaard Thrane ()
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Marcus Petersson: Technical University of Denmark
Franz G. Zingl: Harvard T. H. Chan School of Public Health
Everardo Rodriguez-Rodriguez: Bactolife A/S
Jakob K. H. Rendsvig: Bactolife A/S
Heidi Heinsøe: Bactolife A/S
Emma Wenzel Arendrup: Bactolife A/S
Natalia Mojica: University of Oslo
Dario Segura Peña: University of Oslo
Nikolina Sekulić: University of Oslo
Ute Krengel: University of Oslo
Monica L. Fernández-Quintero: Technical University of Denmark
Timothy P. Jenkins: Technical University of Denmark
Lone Gram: Technical University of Denmark
Matthew K. Waldor: Harvard T. H. Chan School of Public Health
Andreas H. Laustsen: Technical University of Denmark
Sandra Wingaard Thrane: Bactolife A/S

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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 VHHs, 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 VHH 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 VHH prior to V. cholerae infection exhibit a significant reduction in cholera toxin–associated intestinal fluid secretion and diarrhoea. In addition, the bivalent VHH 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.

Date: 2025
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DOI: 10.1038/s41467-025-57945-w

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