A multifunctional anti-O-Antigen human monoclonal antibody protects against Shigella sonnei infection in vivo

• 成果类型: Article
• 署名作者: Ridelfi, Matteo; Vezzani, Giacomo; Roscioli, Emanuele; Batani, Giampiero; Boero, Elena; Nannini, Francesco; Marini, Eleonora; Bhaumik, Ushasi; Desalegn, Girmay; Serpino, Ornella; Molinaro, Antonio; Paciello, Ida; Mugnaini, Chiara; De Santi, Concetta; Maccari, Giuseppe; De Rosa, Antonella; Valensin, Silvia; Duatti, Assia; Di Benedetto, Roberta; Raso, Maria Michelina; Alfini, Renzo; Sammicheli, Chiara; Tavarini, Simona; Quigley, Christina; Podda, Audino; Kabanova, Anna; Andreano, Emanuele; Cardamone, Dario; Gasperini, Gianmarco; Necchi, Francesca; Pizza, Mariagrazia; Martin, Laura B.; Frenck Jr, Robert W.; Grassart, Alexandre; Silipo, Alba; Pasetti, Marcela F.; Scorza, Francesco Berlanda; Giannelli, Carlo; Rossi, Omar; Micoli, Francesca; Sala, Claudia; Rappuoli, Rino
• 署名单位: University of Siena; GlaxoSmithKline; University System of Maryland; University of Maryland Baltimore; University of Naples Federico II; GlaxoSmithKline; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Pasteur Network; Universite de Lille; Institut Pasteur Lille; Imperial College London; United States Pharmacopeia (USP)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11454
• DOI: 10.1073/pnas.2426211122
• 发表日期: 2025-07-29

摘要

Shigellosis is a global public health challenge that mostly affects low-and middle-income countries and causes considerable morbidity and mortality among children under 5 y of age. Multi-and extensively drug-resistant Shigella sonnei strains associated with recent outbreaks in high-income countries exacerbate the problem and have prompted the World Health Organization to include Shigella spp. among the high-risk pathogens for which novel prophylactic and therapeutic tools are urgently needed. Among the most promising and cutting-edge solutions, monoclonal antibodies are gaining considerable attention in the infectious diseases field. Here, we report the discovery of human monoclonal antibodies against S. sonnei, a species whose prevalence is constantly increasing worldwide and is associated with frequent drug-resistant infections. We isolated antibodies generated in response to an experimental S. sonnei vaccine followed by a controlled human infection and screened them by using a panel of high-throughput assays. We identified a molecule which exhibited potent bactericidal activity in vitro, inhibition of invasion of epithelial cells and conferred full protection from S. sonnei infection in vivo. Overall, our study provides a candidate antibody that can rapidly progress to industrial development for application as a prophylactic, therapeutic, and diagnostic tool against shigellosis.