A Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody That Reduces Viral Burden and Disease Severity in Syrian Hamsters

Authors

• Anna C. Fagre, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• John Manhard, AvantGen, Inc. San Diego, CA, United States.
• Rachel Adams, AvantGen, Inc. San Diego, CA, United States.
• Miles Eckley, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• Shijun Zhan, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• Juliette Lewis, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• Savannah M. Rocha, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• Catherine Woods, AvantGen, Inc. San Diego, CA, United States.
• Karina Kuo, AvantGen, Inc. San Diego, CA, United States.
• Wuxiang Liao, AvantGen, Inc. San Diego, CA, United States.
• Lin Li, AvantGen, Inc. San Diego, CA, United States.
• Adam Corper, AvantGen, Inc. San Diego, CA, United States.
• Dilip Challa, AvantGen, Inc. San Diego, CA, United States.
• Emily Mount, AvantGen, Inc. San Diego, CA, United States.
• Christine Tumanut, AvantGen, Inc. San Diego, CA, United States.
• Ronald B. Tjalkens, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• Tawfik Aboellail, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
• Xiaomin Fan, AvantGen, Inc. San Diego, CA, United States.
• Tony Schountz, Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.

Document Type

Article

Abstract

The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.

Keywords

COVID, SARS-CoV-2, coronavirus, monoclonal Ab, therapeutic antibodies

Medical Subject Headings

Animals; Antibodies, Monoclonal (immunology, pharmacology); Antibodies, Neutralizing (immunology, pharmacology); Antibodies, Viral (immunology, pharmacology); COVID-19 (blood, immunology); Chlorocebus aethiops; Humans; Immunoglobulin G (immunology, pharmacology); Male; Mesocricetus; SARS-CoV-2 (immunology); Severity of Illness Index; Vero Cells; Viral Load (drug effects, immunology); COVID-19 Drug Treatment

Publication Date

1-1-2020

Publication Title

Frontiers in immunology

E-ISSN

1664-3224

Volume

11

First Page

614256

PubMed ID

33391285

Digital Object Identifier (DOI)

10.3389/fimmu.2020.614256

Recommended Citation

Fagre, Anna C.; Manhard, John; Adams, Rachel; Eckley, Miles; Zhan, Shijun; Lewis, Juliette; Rocha, Savannah M.; Woods, Catherine; Kuo, Karina; Liao, Wuxiang; Li, Lin; Corper, Adam; Challa, Dilip; Mount, Emily; Tumanut, Christine; Tjalkens, Ronald B.; Aboellail, Tawfik; Fan, Xiaomin; and Schountz, Tony, "A Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody That Reduces Viral Burden and Disease Severity in Syrian Hamsters" (2020). Translational Neuroscience. 2498.
https://scholar.barrowneuro.org/neurobiology/2498