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TitleA chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans.
Journal, issue, pagesSci Transl Med, Vol. 15, Issue 696, Page eade8273, Year 2023
Publish dateMay 17, 2023
AuthorsSaravanan Raju / Lucas J Adams / James T Earnest / Kelly Warfield / Lo Vang / James E Crowe / Daved H Fremont / Michael S Diamond /
PubMed AbstractChikungunya 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 linksSci Transl Med / PubMed:37196061 / PubMed Central
MethodsEM (single particle)
Resolution3.13 - 4.3 Å
Structure data

27763

8dww

EMDB-27763, PDB-8dww:
Chikungunya VLP in complex with neutralizing Fab 506.A08 (asymmetric unit)
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-27764: Chikungunya VLP in complex with neutralizing Fab 506.A08 (icosahedral reconstruction)
Method: EM (single particle) / Resolution: 4.18 Å

27765

8dwx

EMDB-27765, PDB-8dwx:
Chikungunya VLP in complex with neutralizing Fab 506.C01 (asymmetric unit)
Method: EM (single particle) / Resolution: 3.27 Å

EMDB-27766: Chikungunya VLP in complex with neutralizing Fab 506.C01 (icosahedral reconstruction)
Method: EM (single particle) / Resolution: 4.3 Å

27767

8dwy

EMDB-27767, PDB-8dwy:
Chikungunya VLP in complex with neutralizing Fab CHK-265 (asymmetric unit)
Method: EM (single particle) / Resolution: 3.18 Å

EMDB-27768: Chikungunya VLP in complex with neutralizing Fab CHK-265 (icosahedral reconstruction)
Method: EM (single particle) / Resolution: 4.11 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • chikungunya virus strain senegal 37997
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / CSGID / Structural Genomics / Center for Structural Genomics of Infectious Diseases

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