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

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

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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.

Original languageEnglish
Article number1459
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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