A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model

Jakob Kreye ¹, S Momsen Reincke ², Hans-Christian Kornau ³

¹German 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.
²German 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 (BIH), 10178 Berlin, Germany.
³German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
⁴German 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.
⁵Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany, and German Centre for Infection Research (DZIF), 10117 Berlin, Germany.
⁶Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁷Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
⁸Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
⁹Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany; Veterinary Centre for Resistance Research, Freie Universität Berlin, 14163 Berlin, Germany.
¹⁰German Center for Neurodegenerative Diseases (DZNE) Berlin, 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.
¹¹German Center for Neurodegenerative Diseases (DZNE) Berlin, 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 (BIH), 10178 Berlin, Germany.
¹²Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany.
¹³Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Institute of Integrative Neuroanatomy Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹⁴Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
¹⁵Department 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.
¹⁶Department 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; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20359 Hamburg, Germany.
¹⁷Department 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.
¹⁸German Center for Neurodegenerative Diseases (DZNE) Berlin, 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; Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Excellence Cluster NeuroCure Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10785 Berlin, Germany.
¹⁹Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong.
²⁰Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

⁰German 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.

Cell +

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October 15, 2020

View abstract on PubMed

Summary

Researchers identified potent neutralizing antibodies against SARS-CoV-2, the virus causing COVID-19. One antibody, CV07-209, demonstrated strong neutralization and protected hamsters, showing promise for COVID-19 therapeutics.

Area Of Science

Immunology
Virology
Structural Biology

Background

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic disease with respiratory and multi-organ effects.
Understanding virus-neutralizing antibodies and their targets is crucial for COVID-19 treatment and vaccine development.

Purpose Of The Study

To characterize SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) and their epitopes.
To evaluate the therapeutic potential of potent neutralizing mAbs against SARS-CoV-2.

Main Methods

Screening of 598 human mAbs from 10 COVID-19 patients to identify neutralizing antibodies.
Structural analysis of mAb-receptor-binding domain complexes using X-ray crystallography.
In vivo efficacy studies in a hamster model of SARS-CoV-2 infection.

Main Results

Identified 40 strongly neutralizing mAbs, with CV07-209 showing potent neutralization (IC50 = 3.1 ng/mL).
Crystal structures revealed mAbs directly blocking ACE2-receptor attachment.
CV07-209 demonstrated prophylactic and therapeutic protection against SARS-CoV-2 in hamsters, reducing symptoms and lung pathology.

Conclusions

Non-self-reactive, virus-neutralizing mAbs elicited during SARS-CoV-2 infection represent a promising therapeutic strategy.
Characterization of these antibodies provides insights into COVID-19 pathogenesis and antibody-based interventions.

Keywords:

COVID-19 SARS-CoV-2 autoreactivity crystal structures hamster model monoclonal antibody neutralizing antibody post-exposure self-antigens self-reactivity