A Combination of Receptor-Binding Domain and N-Terminal Domain Neutralizing Antibodies Limits the Generation of SARS-CoV-2 Spike Neutralization-Escape Mutants
Denise Haslwanter, M. Eugenia Dieterle, Anna Z. Wec, Cecilia M. O’Brien, Mrunal Sakharkar, Catalina Florez, Karen Tong, C. Garrett Rappazzo, Gorka Lasso, Olivia Vergnolle, Ariel S. Wirchnianski, Robert H. Bortz, Ethan Laudermilch, J. Maximilian Fels, Amanda Mengotto, Ryan J. Malonis, George I. Georgiev, Jose A. Quiroz, Daniel Wrapp, Nianshuang Wang, Kathryn E. Dye, Jason Barnhill, John M. Dye, Jason S. McLellan, Johanna P. Daily, Jonathan R. Lai, Andrew S. Herbert, Laura M. Walker, Kartik Chandran, Rohit K. Jangra
Abstract
The U.S. FDA has issued emergency use authorizations (EUAs) for multiple investigational monoclonal antibody (MAb) therapies for the treatment of mild to moderate COVID-19. These MAb therapeutics are solely targeting the receptor-binding domain of the SARS-CoV-2 spike protein. However, the N-terminal domain of the spike protein also carries crucial neutralizing epitopes. Here, we show that key mutations in the N-terminal domain can reduce the neutralizing capacity of convalescent-phase COVID-19 sera. We report that a combination of two neutralizing antibodies targeting the receptor-binding and N-terminal domains may be beneficial to combat the emergence of virus variants.