Broad sarbecovirus neutralization by combined memory B cell antibodies to ancestral SARS-CoV-2
Cyril Planchais, I. 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, F.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.