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

Cyril Planchais (1) , Ignacio Fernández (2) , Timothée Bruel (3, 4) , Guilherme Dias de Melo (5) , Matthieu Prot (6) , Maxime Beretta (1) , Pablo Guardado-Calvo (2, 7) , Jérémy Dufloo (3, 8) , Luis M Molinos-Albert (1) , Marija Backovic (2) , Jeanne Chiaravalli (9) , Emilie Giraud (9) , Benjamin Vesin (10) , Laurine Conquet (11) , Ludivine Grzelak (3) , Delphine Planas (3) , Isabelle Staropoli (3) , Florence Guivel-Benhassine (3) , Thierry Hieu (12) , Mikaël Boullé (9) , Minerva Cervantes-Gonzalez (13) , Marie-Noëlle Ungeheuer (14) , Pierre Charneau (10) , Sylvie van der Werf (15) , Fabrice Agou (9) , Marie Bartoli , Alpha Diallo , Soizic Le Mestre , Christelle Paul , Ventzislava Petrov-Sanchez , Yazdan Yazdanpanah , Cécile Ficko , Catherine Chirouze , Claire Andrejak , Denis Malvy , François Goehringer , Patrick Rossignol , Tristan Gigante , Morgane Gilg , Bénédicte Rossignol , Manuel Etienne , Marine Beluze , Delphine Bachelet , Krishna Bhavsar , Lila Bouadma , Minerva Cervantes-Gonzalez , Anissa Chair , Charlotte Charpentier , Léo Chenard , Camille Couffignal , Marie-Pierre Debray , Diane Descamps , Xavier Duval , Philippine Eloy , Marina Esposito-Farese , Aline-Marie Florence , Jade Ghosn , Isabelle Hoffmann , Ouifiya Kafif , Antoine Khalil , Nadhem Lafhej , Cédric Laouénan , Samira Laribi , Minh Le , Quentin Le Hingrat , Sophie Letrou , France Mentré , Gilles Peytavin , Valentine Piquard , Carine Roy , Marion Schneider , Richa Su , Coralie Tardivon , Jean-François Timsit , Sarah Tubiana , Benoît Visseaux , Dominique Deplanque , Jean-Sébastien Hulot , Jean-Luc Diehl , Olivier Picone , François Angoulvant , Amal Abrous , Sandrine Couffin-Cadiergues , Fernanda Dias da Silva , Hélène Esperou , Ikram Houas , Salma Jaafoura , Aurélie Papadopoulos , Alexandre Gaymard , Bruno Lina , Manuel Rosa-Calatrava , Céline Dorival , Jérémie Guedj , Guillaume Lingas , Nadège Neant , Laurent Abel , Victoria Manda , Sylvie Behillil , Vincent Enouf , Yves Levy , Aurélie Wiedemann , Laurence Arowas , Blanca Liliana Perlaza , Louise Perrin de Facci , Sophie Chaouche , Linda Sangari , Charlotte Renaudat , Sandrine Fernandes Pellerin , Cassandre van Platen , Nathalie Jolly , Lucie Kuhmel , Valentine Garaud , Hantaniaina Rafanoson , Soazic Gardais , Nathalie de Parseval , Claire Dugast , Caroline Jannet , Sandrine Ropars , Fanny Momboisse , Isabelle Porteret , Isabelle Cailleau , Bruno Hoen , Laura Tondeur , Camille Besombes , Arnaud Fontanet , Jordan D Dimitrov (16) , Etienne Simon-Lorière (6) , Hervé Bourhy (5) , Xavier Montagutelli (11) , Félix A Rey (2) , Olivier Schwartz (3) , Hugo Mouquet (1) , French Covid Cohort Study Group , Corser Study Group

1 Immunologie humorale - Humoral Immunology
2 Virologie Structurale - Structural Virology
3 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
4 VRI - Vaccine Research Institute [Créteil, France]
5 Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology
6 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses
7 UPCité - Université Paris Cité
8 ED562 - BioSPC - École Doctorale Bio Sorbonne Paris Cité [Paris]
9 PF-CCB - Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform
10 Laboratoire commun Pasteur-TheraVectys
11 Génétique de la souris - Mouse Genetics
12 Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases
13 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
14 ICAReB - Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources
15 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
16 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers

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.

Domains: Adaptive immunology; Immunotherapy

Cyril Planchais, Ignacio Fernández, Timothée Bruel, Guilherme Dias de Melo, Matthieu Prot, et al.. Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2. Journal of Experimental Medicine, 2022, 219 (7), pp.e20220638. ⟨10.1084/jem.20220638⟩. ⟨hal-03697587⟩