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<sub>H</sub>Hs, 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<sub>H</sub>H 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<sub>H</sub>H prior to V. cholerae infection exhibit a significant reduction in cholera toxin-associated intestinal fluid secretion and diarrhoea. In addition, the bivalent V<sub>H</sub>H 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.
Authors
- Natalia Mojica (ORCID: https://orcid.org/0009-0007-8836-0201)
- Nikolina Sekulić (ORCID: https://orcid.org/0000-0002-8027-9114)
- Monica L. Fernández‐Quintero (ORCID: https://orcid.org/0000-0002-6811-6283)
- Dario Segura-Peña (ORCID: https://orcid.org/0000-0001-6695-1042)
- Marcus Petersson (ORCID: https://orcid.org/0000-0002-2466-9038)
- Andreas H. Laustsen (ORCID: https://orcid.org/0000-0001-6918-5574)
- Timothy P. Jenkins (ORCID: https://orcid.org/0000-0003-2979-5663)
- Ute Krengel (ORCID: https://orcid.org/0000-0001-6688-8151)
- Franz G. Zingl (ORCID: https://orcid.org/0000-0003-0874-4234)
- Lone Gram (ORCID: https://orcid.org/0000-0002-1076-5723)
- Sandra Wingaard Thrane (ORCID: https://orcid.org/0000-0003-2098-2710)
- Matthew K. Waldor (ORCID: https://orcid.org/0000-0003-1843-7000)
- Jakob K. H. Rendsvig (ORCID: https://orcid.org/0000-0002-4603-9424)
- Emma Wenzel Arendrup (ORCID: https://orcid.org/0009-0006-5709-9322)
- Everardo Remi Rodríguez-Rodríguez (ORCID: https://orcid.org/0000-0002-7445-2830)
- Heidi Heinsøe
Institutions
- Boston University (US)
- University of Copenhagen (DK)
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- University of Oslo (NO)
- Beni American University (NG)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-19
- DOI
- https://doi.org/10.1038/s41467-025-57945-w
- Citations
- 4
- Primary Topic
- Escherichia coli research studies
- Type
- article
- Field-Weighted Citation Impact
- 7.19
Funders
- Life Sciences Research Foundation
- Innovationsfonden
- National Institutes of Health