tetano
Editor, Senior Moderator
Nat Commun
. 2024 Aug 12;15(1):6894.
doi: 10.1038/s41467-024-51046-w. Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways
Matthew Gagne[SUP] 1 [/SUP], Barbara J Flynn[SUP] 1 [/SUP], Christopher Cole Honeycutt[SUP] 1 [/SUP], Dillon R Flebbe[SUP] 1 [/SUP], Shayne F Andrew[SUP] 1 [/SUP], Samantha J Provost[SUP] 1 [/SUP], Lauren McCormick[SUP] 1 [/SUP], Alex Van Ry[SUP] 2 [/SUP], Elizabeth McCarthy[SUP] 1 3 [/SUP], John-Paul M Todd[SUP] 1 [/SUP], Saran Bao[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Shir Marciano[SUP] 4 [/SUP], Yinon Rudich[SUP] 5 [/SUP], Chunlin Li[SUP] 5 [/SUP], Shilpi Jain[SUP] 6 7 8 [/SUP], Bushra Wali[SUP] 6 7 8 [/SUP], Laurent Pessaint[SUP] 2 [/SUP], Alan Dodson[SUP] 2 [/SUP], Anthony Cook[SUP] 2 [/SUP], Mark G Lewis[SUP] 2 [/SUP], Hanne Andersen[SUP] 2 [/SUP], Jiří Zahradník[SUP] 4 [/SUP], Mehul S Suthar[SUP] 6 7 8 9 [/SUP], Martha C Nason[SUP] 10 [/SUP], Kathryn E Foulds[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], Mario Roederer[SUP] 1 [/SUP], Gideon Schreiber[SUP] 4 [/SUP], Robert A Seder[SUP] 11 [/SUP], Daniel C Douek[SUP] 12 [/SUP]
Affiliations
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 Aug 12;15(1):6894.
doi: 10.1038/s41467-024-51046-w. Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways
Matthew Gagne[SUP] 1 [/SUP], Barbara J Flynn[SUP] 1 [/SUP], Christopher Cole Honeycutt[SUP] 1 [/SUP], Dillon R Flebbe[SUP] 1 [/SUP], Shayne F Andrew[SUP] 1 [/SUP], Samantha J Provost[SUP] 1 [/SUP], Lauren McCormick[SUP] 1 [/SUP], Alex Van Ry[SUP] 2 [/SUP], Elizabeth McCarthy[SUP] 1 3 [/SUP], John-Paul M Todd[SUP] 1 [/SUP], Saran Bao[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Shir Marciano[SUP] 4 [/SUP], Yinon Rudich[SUP] 5 [/SUP], Chunlin Li[SUP] 5 [/SUP], Shilpi Jain[SUP] 6 7 8 [/SUP], Bushra Wali[SUP] 6 7 8 [/SUP], Laurent Pessaint[SUP] 2 [/SUP], Alan Dodson[SUP] 2 [/SUP], Anthony Cook[SUP] 2 [/SUP], Mark G Lewis[SUP] 2 [/SUP], Hanne Andersen[SUP] 2 [/SUP], Jiří Zahradník[SUP] 4 [/SUP], Mehul S Suthar[SUP] 6 7 8 9 [/SUP], Martha C Nason[SUP] 10 [/SUP], Kathryn E Foulds[SUP] 1 [/SUP], Peter D Kwong[SUP] 1 [/SUP], Mario Roederer[SUP] 1 [/SUP], Gideon Schreiber[SUP] 4 [/SUP], Robert A Seder[SUP] 11 [/SUP], Daniel C Douek[SUP] 12 [/SUP]
Affiliations
- PMID: 39134521
- DOI: 10.1038/s41467-024-51046-w
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.