TY - JOUR
T1 - Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge
AU - Wen, Jinsheng
AU - Elong Ngono, Annie
AU - Angel Regla-Nava, Jose
AU - Kim, Kenneth
AU - Gorman, Matthew J.
AU - Diamond, Michael S.
AU - Shresta, Sujan
N1 - Funding Information:
This research was funded by NIAID/NIH grants 1R01 AI116813 (to S.S.), and R01 AI104972 and P01 AI106695 (to M.S.D.) and the La Jolla Institute for Allergy & Immunology institutional support to S.S. We would like to thank Anila Mamidi and Matthew Young for breeding mice and managing the survival study.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85033779175&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01669-z
DO - 10.1038/s41467-017-01669-z
M3 - Article
C2 - 29129917
AN - SCOPUS:85033779175
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1459
ER -