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TitlePotent human broadly SARS-CoV-2-neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2.
Journal, issue, pagesJ Exp Med, Vol. 219, Issue 7, Year 2022
Publish dateJul 4, 2022
AuthorsCyril Planchais / Ignacio Fernández / Timothée Bruel / Guilherme Dias de Melo / Matthieu Prot / Maxime Beretta / Pablo Guardado-Calvo / Jérémy Dufloo / Luis M Molinos-Albert / Marija Backovic / Jeanne Chiaravalli / Emilie Giraud / Benjamin Vesin / Laurine Conquet / Ludivine Grzelak / Delphine Planas / Isabelle Staropoli / Florence Guivel-Benhassine / Thierry Hieu / Mikaël Boullé / Minerva Cervantes-Gonzalez / Marie-Noëlle Ungeheuer / Pierre Charneau / Sylvie van der Werf / Fabrice Agou / / / Jordan D Dimitrov / Etienne Simon-Lorière / Hervé Bourhy / Xavier Montagutelli / Félix A Rey / Olivier Schwartz / Hugo Mouquet /
PubMed AbstractMemory 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. ...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.
External linksJ Exp Med / PubMed:35704748 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.3 - 2.89 Å
Structure data

EMDB-14853: SARS-CoV-2 Spike in complex with the neutralizing antibody Cv2.1169
Method: EM (single particle) / Resolution: 2.85 Å

PDB-7qez:
Crystal structure of the SARS-CoV-2 RBD in complex with the ultrapotent antibody CV2.1169 and CR3022
Method: X-RAY DIFFRACTION / Resolution: 2.89 Å

PDB-7qf0:
Crystal structure of the SARS-CoV-2 RBD in complex with the human antibody CV2.2325
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

PDB-7qf1:
Crystal structure of the SARS-CoV-2 RBD in complex with the human antibody CV2.6264
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-SO4:
SULFATE ION

ChemComp-HOH:
WATER

ChemComp-NA:
Unknown entry

ChemComp-CL:
Unknown entry

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / neutralization / antibody / coronavirus

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