Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern.

Autor: Li W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA., Chen Y; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA., Prévost J; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada., Ullah I; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520., Lu M; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA., Gong SY; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada., Tauzin A; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada., Gasser R; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada., Vézina D; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada., Anand SP; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada., Goyette G; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada., Chaterjee D; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada., Ding S; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada., Tolbert WD; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA., Grunst MW; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA., Bo Y; Department of Biochemistry, Microbiology and Immunology, and Center for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Zhang S; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Microbiology, Harvard Medical School, Boston, MA, USA., Richard J; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada., Zhou F; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Huang RK; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Esser L; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Zeher A; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Côté M; Department of Biochemistry, Microbiology and Immunology, and Center for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Kumar P; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520., Sodroski J; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Microbiology, Harvard Medical School, Boston, MA, USA., Xia D; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Uchil PD; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA., Pazgier M; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA., Finzi A; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada., Mothes W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Aug 03. Date of Electronic Publication: 2021 Aug 03.
DOI: 10.1101/2021.08.02.454546
Abstrakt: Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remained effective against emerging variants of concern in vitro and in vivo. CV3-1 bound to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggered potent shedding of the S1 subunit. In contrast, CV3-25 inhibited membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.
Databáze: MEDLINE