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TitleAntigenic landscape of rabies and related lyssaviruses revealed by cryo-EM.
Journal, issue, pagesCell Rep, Vol. 45, Issue 10, Page 117993, Year 2026
Publish dateSep 17, 2026
AuthorsHeather M Callaway / Dawid S Zyla / Kathryn M Hastie / Stephanie S Harkins / Shanika Kothalawalage / Nimasha Samarasinghe / Alexander Flynn / Chitra Hariharan / Jieyun Yin / Davide Corti / Herve Bourhy / Scott K Dessain / Erica Ollmann Saphire /
PubMed AbstractRabies 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 ...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.
External linksCell Rep / PubMed:42758589
MethodsEM (single particle)
Resolution2.92 - 6.69 Å
Structure data

75729

11iw

EMDB-75729, PDB-11iw:
Mouse monoclonal antibody A2 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 3.01 Å

75811

11lp

EMDB-75811, PDB-11lp:
Mouse monoclonal antibody A11 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 2.92 Å

75813

11lq

EMDB-75813, PDB-11lq:
Human monoclonal antibodies 4C12 and 4H3 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 3.24 Å

75814

11lr

EMDB-75814, PDB-11lr:
Human monoclonal antibody 8C5 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 3.16 Å

75815

11ls

EMDB-75815, PDB-11ls:
Human Monoclonal Antibody RVC68 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 3.15 Å

EMDB-75816: Monoclonal antibodies A4, 7E8, and RVC68 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 3.83 Å

EMDB-75817: Human monoclonal antibodies 7E8 and 10H5 in complex with rabies virus glycoprotein
Method: EM (single particle) / Resolution: 6.69 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • lyssavirus rabies
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN/Immune System / Rabies / Rabies virus glycoprotein / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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