Preclinical safety and efficacy of a therapeutic antibody that targets SARS-CoV-2 at the sotrovimab face but is escaped by Omicron.

Autor:	Kreye J; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany.; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; Berlin Institute of Health at Charité, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Reincke SM; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany.; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; Berlin Institute of Health at Charité, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Edelburg S; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Jeworowski LM; Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; German Centre for Infection Research (DZIF), 10117 Berlin, Germany., Kornau HC; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.; Neuroscience Research Center (NWFZ), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany., Trimpert J; Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany., Hombach P; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Halbe S; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Nölle V; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Meyer M; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Kattenbach S; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Sánchez-Sendin E; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany.; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany., Schmidt ML; Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; German Centre for Infection Research (DZIF), 10117 Berlin, Germany., Schwarz T; Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; German Centre for Infection Research (DZIF), 10117 Berlin, Germany., Rose R; Institute for Infection Medicine, Christian-Albrechts-Universität zu Kiel and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany., Krumbholz A; Institute for Infection Medicine, Christian-Albrechts-Universität zu Kiel and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.; Labor Dr. Krause & Kollegen MVZ GmbH, 24106 Kiel, Germany., Merz S; IDEXX Laboratories, 70806 Kornwestheim, Germany., Adler JM; Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany., Eschke K; Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany., Abdelgawad A; Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany., Schmitz D; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.; Neuroscience Research Center (NWFZ), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; Einstein Center for Neuroscience, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; Bernstein Center for Computational Neuroscience, Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Sander LE; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany., Janssen U; Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany., Corman VM; Berlin Institute of Health at Charité, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.; Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.; German Centre for Infection Research (DZIF), 10117 Berlin, Germany.; Labor Berlin-Charité Vivantes GmbH, Berlin, Germany., Prüss H; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany.; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Apr 21; Vol. 26 (4), pp. 106323. Date of Electronic Publication: 2023 Mar 02.
DOI:	10.1016/j.isci.2023.106323
Abstrakt:	The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed in vivo efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study. Although CV38-142 targets the same viral surface as sotrovimab, which maintains activity against Omicron, CV38-142 did not neutralize the Omicron lineages BA.1 and BA.2. These results highlight the contingencies of developing antibody therapeutics in the context of antigenic drift and reinforce the need to develop broadly neutralizing variant-proof antibodies against SARS-CoV-2. Competing Interests: The German Center for Neurodegenerative Diseases (DZNE) and Charité-Universitätsmedizin Berlin have filed a patent application (application number: PCT/EP2021/064,352) on antibodies for the treatment of SARS-CoV-2 infection on which J.K., S.M.R., H.-C.K., E.S.-S., L.E.S., V.M.C., and H.P. are named as inventors. V.M.C. is named together with Euroimmun GmbH on a patent application filed recently regarding the diagnostic of SARS-CoV-2 by antibody testing. S.E., V.N., M.M., S.K., S.H., P.H., and U.J. are employees of Miltenyi Biotec B.V. & Co. KG. (© 2023 The Author(s).)
Databáze:	MEDLINE
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