RBD-based high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways
Gagne, M.; Flynn, B. J.; Honeycutt, C. C.; Flebbe, D. R.; Andrew, S. F.; Provost, S. J.; McCormick, L.; Van Ry, A.; McCarthy, E.; Todd, J.-P. M.; Bao, S.; Teng, I.-T.; Marciano, S.; Rudich, Y.; Li, C.; Pessaint, L.; Dodson, A.; Cook, A.; Lewis, M. G.; Andersen, H.; Zahradnik, J.; Nason, M. C.; Foulds, K. E.; Kwong, P. D.; Roederer, M.; Schreiber, G.; Seder, R. A.; Douek, D. C.
Show abstract
SARS-CoV-2 has the capacity to evolve mutations to escape vaccine-and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool. Here, we challenged rhesus macaques with SARS-CoV-2 Delta and simultaneously treated them with aerosolized RBD-62, a protein developed through multiple rounds of in vitro evolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment gave equivalent protection in upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 did not block the development of memory responses to Delta and did not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.
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