Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy

As Zika virus (ZIKV) emerges into Dengue virus (DENV)-endemic areas, cases of ZIKV infection in DENV-immune pregnant women may rise. Here we show that prior DENV immunity affects maternal and fetal ZIKV infection in pregnancy using sequential DENV and ZIKV infection models. Fetuses in ZIKV-infected DENV-immune dams were normal sized, whereas fetal demise occurred in non-immune dams. Moreover, reduced ZIKV RNA is present in the placenta and fetuses of ZIKV-infected DENV-immune dams. DENV cross-reactive CD8 + T cells expand in the maternal spleen and decidua of ZIKV-infected dams, their depletion increases ZIKV infection in the placenta and fetus, and results in fetal demise. The inducement of cross-reactive CD8 + T cells via peptide immunization or adoptive transfer results in decreased ZIKV infection in the placenta. Prior DENV immunity can protect against ZIKV infection during pregnancy in mice, and CD8 + T cells are sufficient for this cross-protection. This has implications for understanding the natural history of ZIKV in DENV-endemic areas and the development of optimal ZIKV vaccines. Heterologous immunity can confer protection between related viruses. Here the authors show that prior exposure to Dengue virus can protect against subsequent infection with Zika virus in the context of pregnancy, and crucially can prevent demise of the fetus in murine models of infection.