Broad sarbecovirus neutralization by combined memory B cell antibodies to ancestral SARS-CoV-2

联合记忆B细胞抗体对祖先SARS-CoV-2的广泛中和作用

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作者:Cyril Planchais,Ignacio Fernández,Benjamin Chalopin,Timothée Bruel,Pierre Rosenbaum,Maxime Beretta,Jordan D Dimitrov,Laurine Conquet,Flora Donati,Matthieu Prot,Françoise Porrot,Delphine Planas,Isabelle Staropoli,Florence Guivel-Benhassine,Eduard Baquero,Sylvie van der Werf ,Ahmed Haouz,Etienne Simon-Lorière,Xavier Montagutelli,Bernard Maillère,Félix A Rey,Pablo Guardado-Calvo,Hervé Nozach,Olivier Schwartz,Hugo Mouquet

Abstract

Antibodies play a pivotal role in protecting from SARS-CoV-2 infection, but their efficacy is challenged by the continuous emergence of viral variants. In this study, we describe two broadly neutralizing antibodies cloned from the memory B cells of a single convalescent individual after infection with ancestral SARS-CoV-2. Cv2.3194, a resilient class 1 anti-RBD antibody, remains active against Omicron sub-variants up to BA.2.86. Cv2.3132, a near pan-Sarbecovirus neutralizer, targets the heptad repeat 2 membrane proximal region. When combined, Cv2.3194 and Cv2.3132 form a complementary SARS-CoV-2 neutralizing antibody cocktail exhibiting a local dose-dependent synergy. Thus, remarkably robust neutralizing memory B cell antibodies elicited in response to ancestral SARS-CoV-2 infection can withstand viral evolution and immune escape. The cooperative effect of such antibody combination may confer a certain level of protection against the latest SARS-CoV-2 variants.

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