A highly potent antibody effective against SARS-CoV-2 variants of concern

Fenwick, Craig; Turelli, Priscilla; Perez, Laurent; Pellaton, Céline; Esteves-Leuenberger, Line; Farina, Alex; Campos, Jérémy; Lana, Erica; Fiscalini, Flurin; Raclot, Charlène; Pojer, Florence; Lau, Kelvin; Davide, Demurtas; Descatoire, Marc; Joo, Victor S.; Foglierini, Mathilde; Noto, Alessandra; Abdelnabi, Rana; Foo, Caroline S.; Vangeel, Laura; Neyts, Johan; Du, Wenjuan; Bosch, Berend-Jan; Veldman, Geertruida; Leyssen, Pieter; Thiel, Volker; LeGrand, Roger; Lévy, Yves; Trono, Didier; Pantaleo, Giuseppe

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 (VOC) 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.