Discovery and characterization of a pan-betacoronavirus S2-binding antibody.

Autor:	Johnson NV; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA., Wall SC; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA., Kramer KJ; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA., Holt CM; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Periasamy S; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Richardson SI; National Institute for Communicable Diseases of the National Health Laboratory Service, 2131 Johannesburg, South Africa; South African MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa., Manamela NP; National Institute for Communicable Diseases of the National Health Laboratory Service, 2131 Johannesburg, South Africa; South African MRC Antibody Immunity Research Unit, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa., Suryadevara N; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Andreano E; Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy., Paciello I; Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy., Pierleoni G; Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy., Piccini G; VisMederi Research S.r.l., 53100 Siena, Italy., Huang Y; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA; Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Ge P; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA., Allen JD; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA., Uno N; Department of Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USA; Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA., Shiakolas AR; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA., Pilewski KA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA., Nargi RS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Sutton RE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Abu-Shmais AA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA., Parks R; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA., Haynes BF; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Departments of Medicine and Immunology, Duke University, Durham, NC 27710, USA., Carnahan RH; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Crowe JE Jr; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Montomoli E; VisMederi Research S.r.l., 53100 Siena, Italy; VisMederi S.r.l, 53100 Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy., Rappuoli R; Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy., Bukreyev A; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Ross TM; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA; Department of Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44196, USA; Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA; Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA., Sautto GA; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA; Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA. Electronic address: sauttog@ccf.org., McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: jmclellan@austin.utexas.edu., Georgiev IS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 73232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Computer Science, Vanderbilt University, Nashville, TN 37232, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA; Program in Computational Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: ivelin.georgiev@vanderbilt.edu.
Jazyk:	angličtina
Zdroj:	Structure (London, England : 1993) [Structure] 2024 Nov 07; Vol. 32 (11), pp. 1893-1909.e11. Date of Electronic Publication: 2024 Sep 25.
DOI:	10.1016/j.str.2024.08.022
Abstrakt:	The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit. Competing Interests: Declaration of interests A.R.S. and I.S.G. are co-founders of AbSeek Bio. K.J.K., A.R.S., N.V.J., I.S.G., J.S.M., R.H.C., and J.E.C. are listed as inventors on patents filed describing the antibodies discovered here. R.H.C. is an inventor on patents related to other SARS-CoV-2 antibodies. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory has received funding support in sponsored research agreements from AstraZeneca, IDBiologics, and Takeda. The Georgiev laboratory at VUMC has received unrelated funding from Takeda Pharmaceuticals. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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