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. Keywords: immunology; virology.

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