Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2
Authors: Planchais Cyril , Fernández Ignacio , Bruel Timothée , de Melo Guilherme Dias , Prot Matthieu , Beretta Maxime , Guardado-Calvo Pablo , Dufloo Jérémy , Molinos-Albert Luis M. , Backovic Marija , Chiaravalli Jeanne , Giraud Emilie , Vesin Benjamin , Conquet Laurine , Grzelak Ludivine , Planas Delphine , Staropoli Isabelle , Guivel-Benhassine Florence , Hieu Thierry , Boullé Mikaël , Cervantes-Gonzalez Minerva , Ungeheuer Marie-Noëlle , Charneau Pierre , van der Werf Sylvie , Agou Fabrice ,   French COVID Cohort Study Group, 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 ,   CORSER Study Group, 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. , Simon-Lorière Etienne , Bourhy Hervé , Montagutelli Xavier , Rey Félix A. , Schwartz Olivier , Mouquet Hugo 
Published: June 2022

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.