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

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

Edité par CCSD ; Elsevier -

International audience. 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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