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-Structure paper
Title | A chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans. |
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Journal, issue, pages | Sci Transl Med, Vol. 15, Issue 696, Page eade8273, Year 2023 |
Publish date | May 17, 2023 |
Authors | Saravanan Raju / Lucas J Adams / James T Earnest / Kelly Warfield / Lo Vang / James E Crowe / Daved H Fremont / Michael S Diamond / |
PubMed Abstract | Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle- ...Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle-adjuvanted vaccine (PXVX0317) from samples obtained from a phase 2 clinical trial in humans (NCT03483961). Immunization with PXVX0317 induced high levels of neutralizing antibody in serum against CHIKV and circulating antigen-specific B cells up to 6 months after immunization. Monoclonal antibodies (mAbs) generated from peripheral blood B cells of three PXVX0317-vaccinated individuals on day 57 after immunization potently neutralized CHIKV infection, and a subset of these inhibited multiple related arthritogenic alphaviruses. Epitope mapping and cryo-electron microscopy defined two broadly neutralizing mAbs that uniquely bind to the apex of the B domain of the E2 glycoprotein. These results demonstrate the inhibitory breadth and activity of the human B cell response induced by the PXVX0317 vaccine against CHIKV and potentially other related alphaviruses. |
External links | Sci Transl Med / PubMed:37196061 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.13 - 4.3 Å |
Structure data | EMDB-27763, PDB-8dww: EMDB-27764: Chikungunya VLP in complex with neutralizing Fab 506.A08 (icosahedral reconstruction) EMDB-27765, PDB-8dwx: EMDB-27766: Chikungunya VLP in complex with neutralizing Fab 506.C01 (icosahedral reconstruction) EMDB-27767, PDB-8dwy: EMDB-27768: Chikungunya VLP in complex with neutralizing Fab CHK-265 (icosahedral reconstruction) |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / CSGID / Structural Genomics / Center for Structural Genomics of Infectious Diseases |