國家衛生研究院 NHRI:Item 3990099045/12629

NHRI > National Institute of Infectious Diseases and Vaccinology > Chien-Hsiung Pan > Periodical Articles > Item 3990099045/12629

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12629

Title:	Immunodomination of serotype-specific CD4+ T-cell epitopes contributed to the biased immune responses induced by a tetravalent measles-vectored dengue vaccine
Authors:	Lin, TH;Chen, HW;Hsiao, YJ;Yan, JY;Chiang, CY;Chen, MY;Hu, HM;Wu, SH;Pan, CH
Contributors:	National Institute of Infectious Diseases and Vaccinology
Abstract:	Dengue is an emerging mosquito-borne disease, and the use of prophylactic vaccines is still limited. We previously developed a tetravalent dengue vaccine (rMV-TDV) by a recombinant measles virus (MV) vector expressing envelope protein domain III (ED3). In this study, we used dengue-susceptible AG129 mice to evaluate the protective and/or pathogenic immune responses induced by rMV-TDV. Consistent with the previous study, rMV-TDV-immunized mice developed a significant neutralizing antibody response against all serotypes of DENV, as well as a significant IFN-gamma response biased to DENV-3, compared to the vector controls. We further demonstrated that this DENV-3-specific IFN-gamma response was dominated by one CD4(+) T-cell epitope located in E349-363. After DENV-2 challenge, rMV-TDV-immunized mice showed a significantly lower viremia and no inflammatory cytokine increase compared to the vector controls, which had an ~100 times higher viremia and a significant increase in IFN-gamma and TNF-alpha. As a correlate of protection, a robust memory IFN-gamma response specific to DENV-2 was boosted in rMV-TDV-immunized mice after challenge. This result suggested that pre-existing DENV-3-dominated T-cell responses did not cross-react, but a DENV-2-specific IFN-gamma response, which was undetectable during immunization, was recalled. Interestingly, this recalled T-cell response recognized the epitope in the same position as the E349-363 but in the DENV-2 serotype. This result suggested that immunodomination occurred in the CD4(+) T-cell epitopes between dengue serotypes after rMV-TDV vaccination and resulted in a DENV-3-dominated CD4(+) T-cell response. Although the significant increase in IgG against both DENV-2 and -3 suggested that cross-reactive antibody responses were boosted, the increased neutralizing antibodies and IgG avidity still remained DENV-2 specific, consistent with the serotype-specific T cell response post challenge. Our data reveal that immunodomination caused a biased T-cell response to one of the dengue serotypes after tetravalent dengue vaccination and highlight the roles of cross-reactive T cells in dengue protection.
Date:	2020-03-31
Relation:	Frontiers in Immunology. 2020 Mar 31;11:Article number 546.
Link to:	http://dx.doi.org/10.3389/fimmu.2020.00546
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1664-3224&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000526748600001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85083328989
Appears in Collections:	[Chien-Hsiung Pan] Periodical Articles [Hsin-Wei Chen] Periodical Articles

Files in This Item:

File	Description	Size	Format
PUB32300346.pdf		1114Kb	Adobe PDF	285	View/Open

Loading...