SARS-CoV-2's capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs necessitates variant-agnostic therapeutics. This study challenges rhesus macaques with SARS-CoV-2 Delta, treating them with aerosolized RBD-62 (a protein with 100-fold enhanced ACE2 binding affinity). RBD-62 suppressed virus replication in both upper and lower airways without inhibiting virus-specific T- and B-cell responses or eliciting anti-drug immunity, providing proof-of-concept for preventing severe disease from highly virulent variants.

Matthew Gagne, Barbara J. Flynn, Christopher Cole Honeycutt, Dillon R. Flebb, Shayne F. Andrew, Samantha J. Provost, Lauren McCormick, Alex Van Ry, Elizabeth McCarthy, John-Paul M. Todd, Sanan Bao, Ling Teng, Shari Marciano, Yinon Rudich, Chunlin Li, Shilpi Jain, Bashra Wali, Laurent Pessaint, Alan Dodson, Anthony Cook, Mark G. Lewis, Hanne Andersen, Jiří Zahrādník, Mehul S. Suthar, Martha C. Nason, Kathryn E. Foulds, Peter D. Kwong, Mario Roederer, Gideon Schreiber, Robert A. Seder, Daniel C. Douek