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

Author

Listed:
  • Marcus Petersson

    (Technical University of Denmark
    Bactolife A/S)

  • Franz G. Zingl

    (Harvard T. H. Chan School of Public Health
    Brigham and Women’s Hospital
    Harvard Medical School)

  • 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
    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
    Brigham and Women’s Hospital
    Harvard Medical School
    Howard Hughes Medical Institute)

  • Andreas H. Laustsen

    (Technical University of Denmark
    Bactolife A/S)

  • Sandra Wingaard Thrane

    (Bactolife A/S)

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.

Suggested Citation

  • 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 & M, 2025. "Orally delivered toxin–binding protein protects against diarrhoea in a murine cholera model," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57945-w
    DOI: 10.1038/s41467-025-57945-w
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    References listed on IDEAS

    as
    1. Leo Hanke & Hrishikesh Das & Daniel J. Sheward & Laura Perez Vidakovics & Egon Urgard & Ainhoa Moliner-Morro & Changil Kim & Vivien Karl & Alec Pankow & Natalie L. Smith & Bartlomiej Porebski & Oscar , 2022. "A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Fabian Rivera-Chávez & John J. Mekalanos, 2019. "Cholera toxin promotes pathogen acquisition of host-derived nutrients," Nature, Nature, vol. 572(7768), pages 244-248, August.
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