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

• DOI: 10.1126/sciadv.abp9151
• Publication Date: 2022-06-17T17:58:22Z
• Authors: Heather M. Callaway; Dawid Zyla; Florence Larrous; Guilherme Dias de...; Kathryn M. Hastie; Ruben Diaz Avalos; Alyssa Agarwal; Davide Corti; Hervé Bourhy; Erica Ollmann Sap...
• Keywords: 0301 basic medicine; 03 medical and health sciences; [SDV]Life Sciences [q-bio]; Biomedicine and Life Sciences; 3. Good health

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 virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because protein heterogeneous under physiological conditions. Here, we report 3.39 Å cryo–electron microscopy structure trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to quaternary epitope at top RABV-G, bridging domains stabilizing protomers in state. trimerization involves side-to-side interactions between central α helix adjacent loops, rather contacts helices, among fusion loops base. These results provide basis from which develop improved based on stabilized conformation.