Frontiers in Immunology (May 2022)
Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
- Kalyan Pande,
- Scott A. Hollingsworth,
- Miranda Sam,
- Qinshan Gao,
- Sujata Singh,
- Anasuya Saha,
- Karin Vroom,
- Xiaohong Shirley Ma,
- Tres Brazell,
- Dan Gorman,
- Shi-Juan Chen,
- Fahimeh Raoufi,
- Marc Bailly,
- David Grandy,
- Karthik Sathiyamoorthy,
- Lan Zhang,
- Rob Thompson,
- Alan C. Cheng,
- Laurence Fayadat-Dilman,
- Bernhard H. Geierstanger,
- Laura J. Kingsley
Affiliations
- Kalyan Pande
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Scott A. Hollingsworth
- Discovery Chemistry, Merck & Co., Inc., South San Francisco, CA, United States
- Miranda Sam
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Qinshan Gao
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Sujata Singh
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Anasuya Saha
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Karin Vroom
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Xiaohong Shirley Ma
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Tres Brazell
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Dan Gorman
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Shi-Juan Chen
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Fahimeh Raoufi
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Marc Bailly
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- David Grandy
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Karthik Sathiyamoorthy
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Lan Zhang
- Infectious Disease and Vaccine Discovery, Merck & Co., Inc., West Point, PA, United States
- Rob Thompson
- Discovery Chemistry, Merck & Co., Inc., South San Francisco, CA, United States
- Alan C. Cheng
- Discovery Chemistry, Merck & Co., Inc., South San Francisco, CA, United States
- Laurence Fayadat-Dilman
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Bernhard H. Geierstanger
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- Laura J. Kingsley
- Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, United States
- DOI
- https://doi.org/10.3389/fimmu.2022.864775
- Journal volume & issue
-
Vol. 13
Abstract
The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC50 in both pseudo and live virus neutralization assay compared to parental molecules. We also show that hexamer-enhancing mutants improve C1q binding to target surface. To our knowledge, this is the first time this format has been explored for application in viral neutralization and the studies provide proof-of-concept for the use of hexamer-enhanced IgG1 molecules as potential anti-viral therapeutics.
Keywords
