Petersson Marcus, Zingl Franz G, Rodriguez-Rodriguez Everardo, Rendsvig Jakob K H, Heinsøe Heidi, Wenzel Arendrup Emma, Mojica Natalia, Segura Peña Dario, Sekulić Nikolina, Krengel Ute, Fernández-Quintero Monica L, Jenkins Timothy P, Gram Lone, Waldor Matthew K, Laustsen Andreas H, Thrane Sandra Wingaard
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Bactolife A/S, Copenhagen, Denmark.
Nat Commun. 2025 Mar 19;16(1):2722. doi: 10.1038/s41467-025-57945-w.
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 VHs, 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 VH 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 VH prior to V. cholerae infection exhibit a significant reduction in cholera toxin-associated intestinal fluid secretion and diarrhoea. In addition, the bivalent VH 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.
始于1961年的第七次霍乱大流行仍在持续，对公共卫生构成了日益严重的威胁。对于生活在霍乱流行地区的10亿人口而言，需要新的霍乱控制措施，尤其是那些能够低成本生产的措施。作为靶标结合蛋白发挥作用的口服可变区片段（VH）已被提议作为控制胃肠道病原体的一种潜在方法。在此，我们描述了一种可口服递送的二价VH构建体的研发情况，该构建体可与霍乱毒素的B五聚体结合，表明其在小鼠攻毒模型中可抑制毒素活性。在霍乱弧菌感染前给予二价VH的幼鼠，其与霍乱毒素相关的肠液分泌和腹泻显著减少。此外，二价VH使霍乱弧菌在小肠中的定植水平降低了10倍。这种霍乱毒素结合蛋白有望预防与霍乱相关的严重腹泻。
