Development of potent and effective synthetic SARS-CoV-2 neutralizing nanobodies

• Main Authors: Maxwell A. Stefan (Author), Yooli K. Light (Author), Jennifer L. Schwedler (Author), Peter R. McIlroy (Author), Colleen M. Courtney (Author), Edwin A. Saada (Author), Christine E. Thatcher (Author), Ashlee M. Phillips (Author), Feliza A. Bourguet (Author), Catherine M. Mageeney (Author), Summer A. McCloy (Author), Nicole M. Collette (Author), Oscar A. Negrete (Author), Joseph S. Schoeniger (Author), Dina R. Weilhammer (Author), Brooke Harmon (Author)
• Format: Book
• Published: Taylor & Francis Group, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 (VHH)-based antibodies (VHH-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 VHH bacteriophage library, several potent neutralizing VHH-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 VHH-huFc antibody candidates demonstrate that they are prophylactically and therapeutically effective in vivo against wildtype SARS-CoV-2. The identified and characterized VHH-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.

Item Description

10.1080/19420862.2021.1958663
1942-0870
1942-0862