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

Abstract : Rabies infection is nearly 100% lethal if untreated and kills more than 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 Å cryo–electron microscopy structure of trimeric, prefusion 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 α 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 from which to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03698942
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Submitted on : Sunday, June 19, 2022 - 6:16:26 PM
Last modification on : Saturday, June 25, 2022 - 3:44:22 AM

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Heather Callaway, Dawid Zyla, Florence Larrous, Guilherme Dias de Melo, Kathryn Hastie, et al.. Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science Advances , American Association for the Advancement of Science (AAAS), 2022, 8 (24), ⟨10.1126/sciadv.abp9151⟩. ⟨pasteur-03698942⟩

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