2022/08/18 by Weng M. Ng, Sofiya Fedosyuk, Solomon English +7 · 1 voice · 1 citation
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Rabies epidemiology and control #Bacillus and Francisella bacterial research #Poxvirus research and outbreaks
paper · doi:10.1016/j.chom.2022.07.014
openalex publication_date 2022/08/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies.