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

Autor: Gagne M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Flynn BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Honeycutt CC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Flebbe DR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Andrew SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Provost SJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., McCormick L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Van Ry A; Bioqual Inc., Rockville, MD, USA., McCarthy E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Fred Hutch Cancer Center, Seattle, WA, USA., Todd JM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Bao S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Teng IT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Marciano S; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel., Rudich Y; Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot, Israel., Li C; Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot, Israel., Jain S; Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Emory National Primate Research Center, Atlanta, GA, USA., Wali B; Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Emory National Primate Research Center, Atlanta, GA, USA., Pessaint L; Bioqual Inc., Rockville, MD, USA., Dodson A; Bioqual Inc., Rockville, MD, USA., Cook A; Bioqual Inc., Rockville, MD, USA., Lewis MG; Bioqual Inc., Rockville, MD, USA., Andersen H; Bioqual Inc., Rockville, MD, USA., Zahradník J; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel., Suthar MS; Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Emory National Primate Research Center, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA., Nason MC; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Schreiber G; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel., Seder RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. rseder@mail.nih.gov., Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ddouek@mail.nih.gov.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 12; Vol. 15 (1), pp. 6894. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1038/s41467-024-51046-w
Abstrakt: SARS-CoV-2 has the capacity to evolve mutations that 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 that would maintain its efficacy despite the ongoing emergence of new variants. Here, we challenge male rhesus macaques with SARS-CoV-2 Delta-the most pathogenic variant in a highly susceptible animal model. At the time of challenge, we also treat the macaques 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 equivalently suppresses virus replication in both upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 does not block the development of virus-specific T- and B-cell responses and does not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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