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

Autor:	Planchais C; Institut Pasteur, Université Paris Cité, Laboratory of Humoral Immunology, Paris, France.; INSERM U1222, Paris, France., Fernández I; Institut Pasteur, Université Paris Cité, Structural Virology Unit, Paris, France.; CNRS UMR3569, Paris, France., Bruel T; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., de Melo GD; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, France., Prot M; Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, Paris, France., Beretta M; Institut Pasteur, Université Paris Cité, Laboratory of Humoral Immunology, Paris, France.; INSERM U1222, Paris, France., Guardado-Calvo P; Institut Pasteur, Université Paris Cité, Structural Virology Unit, Paris, France.; CNRS UMR3569, Paris, France., Dufloo J; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., Molinos-Albert LM; Institut Pasteur, Université Paris Cité, Laboratory of Humoral Immunology, Paris, France.; INSERM U1222, Paris, France., Backovic M; Institut Pasteur, Université Paris Cité, Structural Virology Unit, Paris, France.; CNRS UMR3569, Paris, France., Chiaravalli J; Institut Pasteur, Université Paris Cité, Chemogenomic and Biological Screening Core Facility, C2RT, Paris, France., Giraud E; Institut Pasteur, Université Paris Cité, Chemogenomic and Biological Screening Core Facility, C2RT, Paris, France., Vesin B; Pasteur-TheraVectys, Paris, France.; Institut Pasteur, Université Paris Cité, Molecular Virology & Vaccinology Unit, Paris, France., Conquet L; Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, Paris, France., Grzelak L; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., Planas D; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., Staropoli I; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., Guivel-Benhassine F; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., Hieu T; Institut Pasteur, Université Paris Cité, Functional Genetics of Infectious Diseases Unit, Paris, France., Boullé M; Institut Pasteur, Université Paris Cité, Chemogenomic and Biological Screening Core Facility, C2RT, Paris, France., Cervantes-Gonzalez M; Department of Epidemiology, Biostatistics and Clinical Research, Assistance Publique-Hôpitaux de Paris, Bichat Claude Bernard University Hospital, INSERM CIC-EC 1425, Paris, France., Ungeheuer MN; Institut Pasteur, Université Paris Cité, Investigation Clinique et Accès aux Ressources Biologiques, Center for Translational Research, Paris, France., Charneau P; Pasteur-TheraVectys, Paris, France.; Institut Pasteur, Université Paris Cité, Molecular Virology & Vaccinology Unit, Paris, France., van der Werf S; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Molecular Genetics of RNA Viruses, Paris, France.; Université de Paris, Paris, France., Agou F; Institut Pasteur, Université Paris Cité, Chemogenomic and Biological Screening Core Facility, C2RT, Paris, France., Dimitrov JD; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France., Simon-Lorière E; Institut Pasteur, Université Paris Cité, G5 Evolutionary Genomics of RNA Viruses, Paris, France., Bourhy H; Institut Pasteur, Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit, Paris, France., Montagutelli X; Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, Paris, France., Rey FA; Institut Pasteur, Université Paris Cité, Structural Virology Unit, Paris, France.; CNRS UMR3569, Paris, France., Schwartz O; CNRS UMR3569, Paris, France.; Institut Pasteur, Université Paris Cité, Virus & Immunity Unit, Paris, France., Mouquet H; Institut Pasteur, Université Paris Cité, Laboratory of Humoral Immunology, Paris, France.; INSERM U1222, Paris, France.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Jul 04; Vol. 219 (7). Date of Electronic Publication: 2022 Jun 15.
DOI:	10.1084/jem.20220638
Abstrakt:	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. (© 2022 Planchais et al.)
Databáze:	MEDLINE
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