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

TitleRBD-based high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways.
Publication TypeJournal Article
Year of Publication2023
AuthorsGagne M, Flynn BJ, Honeycutt CCole, Flebbe DR, Andrew SF, Provost SJ, McCormick L, Van Ry A, McCarthy E, Todd J-PM, Bao S, Teng I-T, Marciano S, Rudich Y, Li C, Pessaint L, Dodson A, Cook A, Lewis MG, Andersen H, ZahradnĂ­k J, Nason MC, Foulds KE, Kwong PD, Roederer M, Schreiber G, Seder RA, Douek DC
JournalbioRxiv
Date Published2023 Jun 12
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.

DOI10.1101/2023.06.09.544432
Alternate JournalbioRxiv
PubMed ID37503026
PubMed Central IDPMC10370179

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