Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways
| Title: | Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways |
|---|---|
| Authors: | Matthew Gagne; Barbara J. Flynn; Christopher Cole Honeycutt; Dillon R. Flebbe; Shayne F. Andrew; Samantha J. Provost; Lauren McCormick; Alex Van Ry; Elizabeth McCarthy; John-Paul M. Todd; Saran Bao; I-Ting Teng; Shir Marciano; Yinon Rudich; Chunlin Li; Shilpi Jain; Bushra Wali; Laurent Pessaint; Alan Dodson; Anthony Cook; Mark G. Lewis; Hanne Andersen; Jiří Zahradník; Mehul S. Suthar; Martha C. Nason; Kathryn E. Foulds; Peter D. Kwong; Mario Roederer; Gideon Schreiber; Robert A. Seder; Daniel C. Douek |
| Source: | Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024) |
| Publisher Information: | Nature Portfolio |
| Publication Year: | 2024 |
| Collection: | Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: | Science |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | https://doi.org/10.1038/s41467-024-51046-w; https://doaj.org/toc/2041-1723; https://doaj.org/article/398a2dfd9ac6483f881f1a81f6f17840 |
| DOI: | 10.1038/s41467-024-51046-w |
| Availability: | https://doi.org/10.1038/s41467-024-51046-w; https://doaj.org/article/398a2dfd9ac6483f881f1a81f6f17840 |
| Accession Number: | edsbas.84618AD2 |
| Database: | BASE |