RBD-based high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways.

Publication Type	Preprint
Authors	Gagne M, Flynn B, Honeycutt C, Flebbe D, Andrew S, Provost S, McCormick L, Van Ry A, McCarthy E, Todd J, Bao S, Teng I, Marciano S, Rudich Y, Li C, Pessaint L, Dodson A, Cook A, Lewis M, Andersen H, Zahradník J, Nason M, Foulds K, Kwong P, Roederer M, Schreiber G, Seder R, Douek D
Journal	bioRxiv
Date Published	06/12/2023
ISSN	2692-8205
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.
DOI	10.1101/2023.06.09.544432
PubMed ID	37503026
PubMed Central ID	PMC10370179