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

作者：Wen, Jinsheng; Ngono, Annie Elong; Regla-Nava, Jose Angel; Kim, Kenneth; Gorman, Matthew J.; Diamond, Michael S.; Shresta, Sujan^*

来源：Nature Communications, 2017, 8(1): 1459.

DOI：10.1038/s41467-017-01669-z

• ANTIBODY-DEPENDENT ENHANCEMENT
• MOUSE MODEL
• INFECTION
• RESPONSES
• CD4(+)
• PATHOGENESIS
• LYMPHOCYTES
• INSIGHTS
• DISEASE
• NEUTRALIZATION

Zika virus (ZIKV) and dengue virus (DENV) are antigenically related flaviviruses that share cross-reactivity in antibody and T cell responses, and co-circulate in increasing numbers of countries. Whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection during sequential infection of the same host is unknown. Here, we show that DENV-immune Ifnar1(-/-) or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and pathogenesis. Adoptive transfer and cell depletion studies demonstrate that DENV-immune CD8(+) T cells predominantly mediate cross-protective responses to ZIKV. In contrast, passive transfer studies suggest that DENV-immune serum does not protect against ZIKV infection. Thus, CD8(+) T cell immunity generated during primary DENV infection can confer protection against secondary ZIKV infection in mice. Further optimization of current DENV vaccines for T cell responses might confer cross-protection and prevent antibody-mediated enhancement of ZIKV infection.

• 出版日期2017-11-13
• 单位温州医科大学