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bioRxiv · 10.1101/2021.11.16.468852

Structure of the rabies virus glycoprotein trimer bound to a pre-fusion specific neutralizing antibody

Callaway, H. M.·Zyla, D.·Hastie, K. M.·Avalos, R. D.·Agarwal, A.·Bourhy, H.·Corti, D.·Saphire, E. O.
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Abstract

Rabies infection is nearly 100% lethal if untreated and kills over 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39[A] cryo-EM structure of trimeric, pre-fusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central -helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation. One sentence summaryWe report the structure and trimeric interface of pre-fusion rabies virus glycoprotein bound to the neutralizing antibody RVA122.

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Callaway, H. M., Zyla, D., Hastie, K. M., Avalos, R. D., Agarwal, A., Bourhy, H., Corti, D., Saphire, E. O.. 2021-11-16. Structure of the rabies virus glycoprotein trimer bound to a pre-fusion specific neutralizing antibody. https://doi.org/10.1101/2021.11.16.468852

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