iScience (Jul 2024)
Broad sarbecovirus neutralization by combined memory B cell antibodies to ancestral SARS-CoV-2
- 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
Affiliations
- Cyril Planchais
- Institut Pasteur, Université Paris Cité, INSERM U1222, Humoral Immunology Unit, 75015 Paris, France
- Ignacio Fernández
- Institut Pasteur, Université Paris Cité, Structural Virology Unit, 75015 Paris, France; CNRS UMR3569, 75015 Paris, France
- Benjamin Chalopin
- CEA, INRAE, Medicines and Healthcare Technologies Department, SIMoS, Université Paris-Saclay, 91190 Gif-sur-Yvette, France
- Timothée Bruel
- CNRS UMR3569, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, 75015 Paris, France
- Pierre Rosenbaum
- Institut Pasteur, Université Paris Cité, INSERM U1222, Humoral Immunology Unit, 75015 Paris, France
- Maxime Beretta
- Institut Pasteur, Université Paris Cité, INSERM U1222, Humoral Immunology Unit, 75015 Paris, France
- Jordan D. Dimitrov
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, 75006 Paris, France
- Laurine Conquet
- Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, 75015 Paris, France
- Flora Donati
- Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, 75015 Paris, France; National Reference Center for Respiratory Viruses, Institut Pasteur, 75015 Paris, France
- Matthieu Prot
- Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, 75015 Paris, France
- Françoise Porrot
- CNRS UMR3569, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, 75015 Paris, France
- Delphine Planas
- CNRS UMR3569, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, 75015 Paris, France
- Isabelle Staropoli
- CNRS UMR3569, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, 75015 Paris, France
- Florence Guivel-Benhassine
- CNRS UMR3569, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, 75015 Paris, France
- Eduard Baquero
- Institut Pasteur, Université Paris Cité, Structural Virology Unit, 75015 Paris, France; CNRS UMR3569, 75015 Paris, France
- Sylvie van der Werf
- CNRS UMR3569, 75015 Paris, France; National Reference Center for Respiratory Viruses, Institut Pasteur, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Molecular Genetics of RNA Viruses, 75015 Paris, France
- Ahmed Haouz
- Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Cristallography Platform-C2RT, 75015 Paris, France
- Etienne Simon-Lorière
- Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, 75015 Paris, France; National Reference Center for Respiratory Viruses, Institut Pasteur, 75015 Paris, France
- Xavier Montagutelli
- Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, 75015 Paris, France
- Bernard Maillère
- CEA, INRAE, Medicines and Healthcare Technologies Department, SIMoS, Université Paris-Saclay, 91190 Gif-sur-Yvette, France
- Félix A. Rey
- Institut Pasteur, Université Paris Cité, Structural Virology Unit, 75015 Paris, France; CNRS UMR3569, 75015 Paris, France
- Pablo Guardado-Calvo
- Institut Pasteur, Université Paris Cité, Structural Virology Unit, 75015 Paris, France; CNRS UMR3569, 75015 Paris, France
- Hervé Nozach
- CEA, INRAE, Medicines and Healthcare Technologies Department, SIMoS, Université Paris-Saclay, 91190 Gif-sur-Yvette, France
- Olivier Schwartz
- CNRS UMR3569, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, 75015 Paris, France
- Hugo Mouquet
- Institut Pasteur, Université Paris Cité, INSERM U1222, Humoral Immunology Unit, 75015 Paris, France; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 7
p. 110354
Abstract
Summary: 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.
