Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2-Reference-Cited by-全球学者库

Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2

Published:2022-06-15 Issue:7 Volume:219 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Planchais Cyril¹²^ORCID,Fernández Ignacio³⁴^ORCID,Bruel Timothée⁴⁵^ORCID,de Melo Guilherme Dias⁶^ORCID,Prot Matthieu⁷^ORCID,Beretta Maxime¹²^ORCID,Guardado-Calvo Pablo³⁴^ORCID,Dufloo Jérémy⁴⁵^ORCID,Molinos-Albert Luis M.¹²^ORCID,Backovic Marija³⁴^ORCID,Chiaravalli Jeanne⁸^ORCID,Giraud Emilie⁸^ORCID,Vesin Benjamin⁹¹⁰^ORCID,Conquet Laurine¹¹^ORCID,Grzelak Ludivine⁴⁵^ORCID,Planas Delphine⁴⁵^ORCID,Staropoli Isabelle⁴⁵^ORCID,Guivel-Benhassine Florence⁴⁵^ORCID,Hieu Thierry¹²^ORCID,Boullé Mikaël⁸^ORCID,Cervantes-Gonzalez Minerva¹³^ORCID,Ungeheuer Marie-Noëlle¹⁴^ORCID,Charneau Pierre⁹¹⁰^ORCID,van der Werf Sylvie⁴¹⁵¹⁶,Agou Fabrice⁸^ORCID,Bartoli Marie,Diallo Alpha,Le Mestre Soizic,Paul Christelle,Petrov-Sanchez Ventzislava,Yazdanpanah Yazdan,Ficko Cécile,Chirouze Catherine,Andrejak Claire,Malvy Denis,Goehringer François,Rossignol Patrick,Gigante Tristan,Gilg Morgane,Rossignol Bénédicte,Etienne Manuel,Beluze Marine,Bachelet Delphine,Bhavsar Krishna,Bouadma Lila,Cervantes-Gonzalez Minerva,Chair Anissa,Charpentier Charlotte,Chenard Léo,Couffignal Camille,Debray Marie-Pierre,Descamps Diane,Duval Xavier,Eloy Philippine,Esposito-Farese Marina,Florence Aline-Marie,Ghosn Jade,Hoffmann Isabelle,Kafif Ouifiya,Khalil Antoine,Lafhej Nadhem,Laouénan Cédric,Laribi Samira,Le Minh,Le Hingrat Quentin,Letrou Sophie,Mentré France,Peytavin Gilles,Piquard Valentine,Roy Carine,Schneider Marion,Su Richa,Tardivon Coralie,Timsit Jean-François,Tubiana Sarah,Visseaux Benoît,Deplanque Dominique,Hulot Jean-Sébastien,Diehl Jean-Luc,Picone Olivier,Angoulvant François,Abrous Amal,Couffin-Cadiergues Sandrine,Da Silva Fernanda Dias,Esperou Hélène,Houas Ikram,Jaafoura Salma,Papadopoulos Aurélie,Gaymard Alexandre,Lina Bruno,Rosa-Calatrava Manuel,Dorival Céline,Guedj Jérémie,Lingas Guillaume,Neant Nadège,Abel Laurent,Manda Victoria,Behillil Sylvie,Enouf Vincent,Levy Yves,Wiedemann Aurélie,Arowas Laurence,Perlaza Blanca Liliana,Perrin de Facci Louise,Chaouche Sophie,Sangari Linda,Renaudat Charlotte,Fernandes Pellerin Sandrine,van Platen Cassandre,Jolly Nathalie,Kuhmel Lucie,Garaud Valentine,Rafanoson Hantaniaina,Gardais Soazic,de Parseval Nathalie,Dugast Claire,Jannet Caroline,Ropars Sandrine,Momboisse Fanny,Porteret Isabelle,Cailleau Isabelle,Hoen Bruno,Tondeur Laura,Besombes Camille,Fontanet Arnaud,Dimitrov Jordan D.¹⁷^ORCID,Simon-Lorière Etienne⁷^ORCID,Bourhy Hervé⁶^ORCID,Montagutelli Xavier¹¹^ORCID,Rey Félix A.³⁴^ORCID,Schwartz Olivier⁴⁵^ORCID,Mouquet Hugo¹²^ORCID, ,

Affiliation:

1. Institut Pasteur, Université Paris Cité, Laboratory of Humoral Immunology, Paris, France 1

2. INSERM U1222, Paris, France 2

3. Institut Pasteur, Université Paris Cité, Structural Virology Unit, Paris, France 3

4. CNRS UMR3569, Paris, France 4

5. Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France 5

6. Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, France 6

7. Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, Paris, France 7

8. Institut Pasteur, Université Paris Cité, Chemogenomic and Biological Screening Core Facility, C2RT, Paris, France 8

9. Pasteur-TheraVectys, Paris, France 9

10. Institut Pasteur, Université Paris Cité, Molecular Virology & Vaccinology Unit, Paris, France 10

11. Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, Paris, France 11

12. Institut Pasteur, Université Paris Cité, Functional Genetics of Infectious Diseases Unit, Paris, France 12

13. Department of Epidemiology, Biostatistics and Clinical Research, Assistance Publique-Hôpitaux de Paris, Bichat Claude Bernard University Hospital, INSERM CIC-EC 1425, Paris, France 13

14. Institut Pasteur, Université Paris Cité, Investigation Clinique et Accès aux Ressources Biologiques, Center for Translational Research, Paris, France 14

15. Institut Pasteur, Université Paris Cité, Molecular Genetics of RNA Viruses, Paris, France 15

16. Université de Paris, Paris, France 16

17. Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France 17

Abstract

Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor-binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.

Funder

Institut Pasteur

French Government’s Investissements d’Avenir program

Institut national de la santé et de la recherche médicale

REsearch & ACtion emergING infectious diseases (REACTing) consortium

Ministry of Health and Social Affairs

Ministry of Higher Education and Research

Agence Nationale de la Recherche

European Commission

Fondation de France

Agence Nationale de Recherches sur le Sida et les Hépatites Virales

Programme hospitalier de recherche clinique