Development of potent and effective synthetic SARS-CoV-2 neutralizing nanobodies. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Stefan, Maxwell A.; Light, Yooli K.; Schwedler, Jennifer L.; McIlroy, Peter R.; Courtney, Colleen M.; Saada, Edwin A.; Thatcher, Christine E.; Phillips, Ashlee M.; Bourguet, Feliza A.; Mageeney, Catherine M.; McCloy, Summer A.; Collette, Nicole M.; Negrete, Oscar A.; Schoeniger, Joseph S.; Weilhammer, Dina R.; Harmon, Brooke
• Is Part Of: MAbs. Volume 13:Issue 1(2021)
• Publication Date: 2021-01-01
• Subjects: Nanobody -- neutralizing antibody -- phage display -- COVID-19 -- SARS-CoV-2; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2021.1958663
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: The respiratory virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected nearly every aspect of life worldwide, claiming the lives of over 3.9 million people globally, at the time of this publication. Neutralizing humanized nanobody (VH H)-based antibodies (VH H-huFc) represent a promising therapeutic intervention strategy to address the current SARS-CoV-2 pandemic and provide a powerful toolkit to address future virus outbreaks. Using a synthetic, high-diversity VH H bacteriophage library, several potent neutralizing VH H-huFc antibodies were identified and evaluated for their capacity to tightly bind to the SARS-CoV-2 receptor-binding domain, to prevent binding of SARS-CoV-2 spike (S) to the cellular receptor angiotensin-converting enzyme 2, and to neutralize viral infection. Preliminary preclinical evaluation of multiple VH H-huFc antibody candidates demonstrate that they are prophylactically and therapeutically effective in vivo against wildtype SARS-CoV-2. The identified and characterized VH H-huFc antibodies described herein represent viable candidates for further preclinical evaluation and another tool to add to our therapeutic arsenal to address the COVID-19 pandemic.