國家衛生研究院 NHRI:Item 3990099045/9450
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    题名: The immunodominance change and protection of CD4+ T-cell responses elicited by an envelope protein domain III-based tetravalent dengue vaccine in mice
    作者: Chen, HW;Hu, HM;Wu, SH;Chiang, CY;Hsiao, YJ;Wu, CK;Hsieh, CH;Chung, HH;Chong, P;Leng, CH;Pan, CH
    贡献者: Division of Vaccine Research and Development
    摘要: Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3) is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4), we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost). A significant serotype-dependent IFN-gamma or IL-4 response was observed in mice immunized with either the DNA or protein vaccine. The IFN-gamma response was dominant to DENV-1 to 3, whereas the IL-4 response was dominant to DENV-4. Although the similar IgG titers for the four serotypes were observed in mice immunized with the tetravalent vaccines, the neutralizing antibody titers varied and followed the order of 2 = 3>1>4. Interestingly, the lower IFN-gamma response to DENV-4 is attributable to the immunodominance change between two CD4+ T-cell epitopes; one T-cell epitope located at E349-363 of DENV-1 to 3 was more immunogenic than the DENV-4 epitope E313-327. Despite DENV-4 specific IFN-gamma responses were suppressed by immunodominance change, either DENV-4-specific IFN-gamma or neutralizing antibody responses were still recalled after DENV-4 challenge and contributed to virus clearance. Immunization with the prime-boost elicited both IFN-gamma and neutralizing antibody responses and provided better protection than either DNA or protein immunization. Our findings shed light on how ED3-based tetravalent dengue vaccines sharpen host CD4 T-cell responses and contribute to protection against dengue virus.
    日期: 2015-12-29
    關聯: PLoS ONE. 2015 Dec 29;10(12):Article number e0145717.
    Link to: http://dx.doi.org/10.1371/journal.pone.0145717
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000367481900073
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84957579705
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