National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
75N93019C00062
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
HHSN272201700060C
United States
Citation
Journal: Sci Transl Med / Year: 2023 Title: A chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans. Authors: Saravanan Raju / Lucas J Adams / James T Earnest / Kelly Warfield / Lo Vang / James E Crowe / Daved H Fremont / Michael S Diamond / 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.
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