11LR

Human monoclonal antibody 8C5 in complex with rabies virus glycoprotein

Summary for 11LR

• Entry DOI: 10.2210/pdb11lr/pdb
• EMDB information: 75814
• Descriptor: Monoclonal Antibody RVA122 Heavy Chain, Glycoprotein, Monoclonal Antibody RVA122 Light Chain, ... (6 entities in total)
• Functional Keywords: rabies, rabies virus glycoprotein, antibody, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 15
• Total formula weight: 467185.07

Authors

Callaway, H.M.,Zyla, D.,Hastie, K.,Harkins, S.,Kothalawalage, S.,Samarasinghe, S.,Flynn, A.,Hariharan, C.,Yin, J.,Corti, D.,Bouhry, H.,Dessain, S.,Saphire, E.O. (deposition date: 2026-03-03, release date: 2026-08-19, Last modification date: 2026-09-30)

Primary citation

Callaway, H.M.,Zyla, D.S.,Hastie, K.M.,Harkins, S.S.,Kothalawalage, S.,Samarasinghe, N.,Flynn, A.,Hariharan, C.,Yin, J.,Corti, D.,Bourhy, H.,Dessain, S.K.,Saphire, E.O.
Antigenic landscape of rabies and related lyssaviruses revealed by cryo-EM.
Cell Rep, 45:117993-117993, 2026

PubMed Abstract: Rabies continues to kill over 60,000 people per year despite life-saving vaccines and post-exposure treatments and costs billions of dollars in prevention and treatment. Preventing rabies deaths and reducing the global economic burden of the virus will require both developing a monoclonal antibody cocktail to replace human serum in treatment and improving rabies vaccines to elicit long-lasting protection. Here, we solve nine cryo-electron microscopy (cryo-EM) structures of neutralizing monoclonal antibodies (mAbs) in complex with the rabies virus glycoprotein (RABV-G). The nine structures span three known antigenic sites plus two additional antigenic sites, not among the five classically identified sites. We find that these antigenic sites, V and VI, are broadly cross-reactive across lyssaviruses, whereas immunodominant sites II/IV and III are rabies specific. Across the mAb panel, fusion inhibition and binding affinity correlate best with neutralization. Together, these results provide a roadmap for structure-guided vaccine and therapeutic antibody design for rabies and related lyssaviruses.

PubMed: 42758589
DOI: 10.1016/j.celrep.2026.117993

Experimental method

ELECTRON MICROSCOPY (3.16 Å)