A multifunctional anti-O-Antigen human monoclonal antibody protects against Shigella sonnei infection in vivo
- Matteo Ridelfi
- Giacomo Vezzani
- Emanuele Roscioli
- Giampiero Batani
- Elena Boero
- Francesco Nannini
- Eleonora Marini
- Ushasi Bhaumik
- Girmay Desalegn
- Ornella Serpino
- Antonio Molinaro
- Ida Paciello
- Chiara Mugnaini
- Concetta De Santi
- Giuseppe Maccari
- Antonella De Rosa
- Silvia Valensin
- Assia Duatti
- Roberta Di Benedetto
- Maria Michelina Raso
- Renzo Alfini
- Chiara Sammicheli
- Simona Tavarini
- Christina Quigley
- Audino Podda
- Anna Kabanova
- Emanuele Andreano
- Dario Cardamone
- Gianmarco Gasperini
- Francesca Necchi
- Mariagrazia Pizza
- Laura B. Martin
- Robert W. Frenck
- Alexandre Grassart
- Alba Silipo
- Marcela F. Pasetti
- Francesco Berlanda Scorza
- Carlo Giannelli
- Omar Rossi
- Francesca Micoli
- Claudia Sala
- Rino Rappuoli
2025-07-23
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.