A multifunctional anti-O-Antigen human monoclonal antibody protects against <i>Shigella sonnei</i> infection in vivo
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (42)
Matteo Ridelfi
Giacomo Vezzani
GSK Vaccines Institute for Global Health
Emanuele Roscioli
Giampiero Batani
Elena Boero
GSK Vaccines Institute for Global Health
Francesco Nannini
Monoclonal Antibody Discovery Laboratory, Fondazione Toscana Life Sciences
Eleonora Marini
Monoclonal Antibody Discovery Laboratory, Fondazione Toscana Life Sciences
Ushasi Bhaumik
Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
Girmay Desalegn
Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
Ornella Serpino
Dipartimento di Scienze Chimiche, Università degli Studi di Napoli Federico II
Antonio Molinaro
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital
Ida Paciello
Chiara Mugnaini
Concetta De Santi
Giuseppe Maccari
Antonella De Rosa
Fondazione Toscana Life Sciences
Silvia Valensin
Fondazione Toscana Life Sciences
Assia Duatti
GSK Vaccines Institute for Global Health
Roberta Di Benedetto
GSK Vaccines Institute for Global Health
Maria Michelina Raso
GSK Vaccines Institute for Global Health
Renzo Alfini
GSK Vaccines Institute for Global Health
Chiara Sammicheli
GlaxoSmithKline
Simona Tavarini
GlaxoSmithKline
Christina Quigley
Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center
Audino Podda
GSK Vaccines Institute for Global Health
Anna Kabanova
Emanuele Andreano
Monoclonal Antibody Discovery Laboratory, Fondazione Toscana Life Sciences
Dario Cardamone
Gianmarco Gasperini
GSK Vaccines Institute for Global Health
Francesca Necchi
GSK Vaccines Institute for Global Health
Mariagrazia Pizza
GSK Vaccines Institute for Global Health
Laura B. Martin
GSK Vaccines Institute for Global Health
Robert W. Frenck
Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center
Alexandre Grassart
Institut Pasteur de Lille
Alba Silipo
Dipartimento di Scienze Chimiche, Università degli Studi di Napoli Federico II
Marcela F. Pasetti
Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine
Francesco Berlanda Scorza
GSK Vaccines Institute for Global Health
Carlo Giannelli
GSK Vaccines Institute for Global Health
Omar Rossi
GSK Vaccines Institute for Global Health
Francesca Micoli
GSK Vaccines Institute for Global Health
Claudia Sala
Rino Rappuoli