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

Jakob Kreye; S Momsen Reincke; Stefan Edelburg; Lara M Jeworowski; Hans-Christian Kornau; Jakob Trimpert; Peter Hombach; Sophia Halbe; Volker Nölle; Martin Meyer; Stefanie Kattenbach; Elisa Sánchez-Sendin; Marie L Schmidt; Tatjana Schwarz; Ruben Rose; Andi Krumbholz; Sophie Merz; Julia M Adler; Kathrin Eschke; Azza Abdelgawad; Dietmar Schmitz; Leif E Sander; Uwe Janssen; Victor M Corman; Harald Prüss

doi:10.1016/j.isci.2023.106323

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

iScience. 2023 Apr 21;26(4):106323. doi: 10.1016/j.isci.2023.106323. Epub 2023 Mar 2.

Authors

Jakob Kreye^{1

2

3

4

5}, S Momsen Reincke^{1

2

3

5}, Stefan Edelburg⁶, Lara M Jeworowski^{7

8}, Hans-Christian Kornau^{1

9}, Jakob Trimpert¹⁰, Peter Hombach⁶, Sophia Halbe⁶, Volker Nölle⁶, Martin Meyer⁶, Stefanie Kattenbach⁶, Elisa Sánchez-Sendin^{1

2

3}, Marie L Schmidt^{7

8}, Tatjana Schwarz^{7

8}, Ruben Rose¹¹, Andi Krumbholz^{11

12}, Sophie Merz¹³, Julia M Adler¹⁰, Kathrin Eschke¹⁰, Azza Abdelgawad¹⁰, Dietmar Schmitz^{1

9

14

15

16}, Leif E Sander¹⁷, Uwe Janssen⁶, Victor M Corman^{5

7

8

18}, Harald Prüss^{1

2

3}

Affiliations

¹ German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany.
² Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany.
³ 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.
⁴ Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
⁵ Berlin Institute of Health at Charité, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
⁶ Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.
⁷ Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
⁸ German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
⁹ Neuroscience Research Center (NWFZ), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹⁰ Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
¹¹ Institute for Infection Medicine, Christian-Albrechts-Universität zu Kiel and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
¹² Labor Dr. Krause & Kollegen MVZ GmbH, 24106 Kiel, Germany.
¹³ IDEXX Laboratories, 70806 Kornwestheim, Germany.
¹⁴ Einstein Center for Neuroscience, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹⁵ NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹⁶ Bernstein Center for Computational Neuroscience, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
¹⁷ 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.
¹⁸ Labor Berlin-Charité Vivantes GmbH, Berlin, Germany.

Abstract

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.

Keywords: Immunology; Virology.