Dengue virus-reactive CD8⁺ T cells mediate cross-protection against subsequent Zika virus challenge.

Jinsheng Wen et al., Nat Commun. 2017; 8(1):1459.

Speaker: Yu-San Kao（高于珊）                   Time: 14:00~15:00, Mar. 28, 2018

Commentator: Dr. Hsiao-Sheng Liu（劉校生 老師）  Place: Room 601

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Antibody-dependent enhancement (ADE) has been implicated in more severe forms of flavivirus disease due to preexisting flavivirus immunity, and ZIKV is presently circulating in areas that DENV are highly endemic. Accordingly, a number of studies attempted to answer whether the DENV-ZIKV heterologous immune responses may provide protection or contribute to pathogenesis. Previous studies showed that some DENV antibodies are cross-reactive to ZIKV and can enhance ZIKV infection at specific concentrations in passive transfer experiments using plasma from DENV immune host. In this study, the authors revealed whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection in the same host with sequential infection. The results showed that DENV-immune Ifnar1^-/- or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and reduce ZIKV burden. Furthermore, they demonstrated that DENV-immune CD8⁺ T cells predominantly mediate cross-protective responses to ZIKV by adoptive transfer and cell depletion experiments. They also confirmed that DENV-immune serum does not protect against ZIKV infection by passive transfer experiments. Collectively, their work indicates DENV immune CD8⁺ T cells but not DENV-reactive antibodies in serum can confer cross-protection against lethal ZIKV infection in mice. Their results highlight the strategy of DENV vaccine optimization by inducing robust CD8⁺ T cell responses to offer cross-protection and prevent ADE of ZIKV infection.

References：

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