A highly potent antibody effective against SARS-CoV-2 variants of concern
Craig Fenwick, Priscilla Turelli, Laurent Perez, Céline Pellaton, Line Esteves-Leuenberger, Alex Farina, Jérémy Campos, Erica Lana, Flurin Fiscalini, Charlène Raclot, Florence Pojer, Kelvin Lau, Davide Demurtas, Marc Descatoire, Victor Joo, Mathilde Foglierini, Alessandra Noto, Rana Abdelnabi, Caroline S. Foo, Laura Vangeel, Johan Neyts, Wenjuan Du, Berend‐Jan Bosch, Geertruida M. Veldman, Pieter Leyssen, Volker Thiel, R. Legrand, Yves Lévy, Didier Trono, Giuseppe Pantaleo
Abstract
Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.