iScience (Sep 2022)
Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways
- Fangzhu Zhao,
- Celina Keating,
- Gabriel Ozorowski,
- Namir Shaabani,
- Irene M. Francino-Urdaniz,
- Shawn Barman,
- Oliver Limbo,
- Alison Burns,
- Panpan Zhou,
- Michael J. Ricciardi,
- Jordan Woehl,
- Quoc Tran,
- Hannah L. Turner,
- Linghang Peng,
- Deli Huang,
- David Nemazee,
- Raiees Andrabi,
- Devin Sok,
- John R. Teijaro,
- Timothy A. Whitehead,
- Andrew B. Ward,
- Dennis R. Burton,
- Joseph G. Jardine
Affiliations
- Fangzhu Zhao
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Celina Keating
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Gabriel Ozorowski
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Namir Shaabani
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Irene M. Francino-Urdaniz
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA
- Shawn Barman
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Oliver Limbo
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI, New York, NY 10004, USA
- Alison Burns
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Panpan Zhou
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Michael J. Ricciardi
- Department of Pathology, George Washington University, Washington, DC 20052, USA
- Jordan Woehl
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI, New York, NY 10004, USA
- Quoc Tran
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI, New York, NY 10004, USA
- Hannah L. Turner
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Linghang Peng
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Deli Huang
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- David Nemazee
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Raiees Andrabi
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
- Devin Sok
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI, New York, NY 10004, USA
- John R. Teijaro
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Timothy A. Whitehead
- Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305, USA
- Andrew B. Ward
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Dennis R. Burton
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Corresponding author
- Joseph G. Jardine
- IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI, New York, NY 10004, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 9
p. 104914
Abstract
Summary: The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here, we used a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased in vitro functional activity in terms of neutralization potency and/or breadth of neutralization against viral variants. Deep mutational scanning revealed that higher binding affinity reduces the total number of viral escape mutations. Studies in the Syrian hamster model showed two examples where the affinity-matured antibody provided superior protection compared to the parental antibody. These data suggest that monoclonal antibodies for antiviral indications would benefit from affinity maturation to reduce viral escape pathways and appropriate affinity maturation in vaccine immunization could help resist viral variation.
