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<p>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 <i>V. cholerae</i> infection exhibit a significant reduction in cholera toxin–associated intestinal fluid secretion and diarrhoea. In addition, the bivalent V<sub>H</sub>H reduces <i>V. cholerae</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月19日

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  • 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,
  • Sandra Wingaard Thrane

摘要

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.