Time elapsed between Zika and Dengue infections improves the immune response against Dengue without viremia enhancement in rhesus macaques

The role of a previous Zika virus (ZIKV) immunity on subsequent Dengue virus (DENV) infections is poorly understood. This is relevant to anticipate the dynamics of forthcoming DENV epidemics in areas with previous ZIKV exposure. It is still uncertain if the immunity conferred by the recent ZIKV epidemic may contribute to protection or worsening DENV cases severity. Accordingly, we have studied the effect of ZIKV infection with various strains on subsequent DENV immune response after 10 and 2 months of ZIKV infection. Our results in non-human primates showed that a subsequent DENV infection in animals with early- and middle-convalescent periods to ZIKV do not promote an increase in DENV viremia nor pro-inflammatory status. We found that previous ZIKV exposure improves the antibody and cell-mediated immune responses against DENV and that the time interval between infections impacted the magnitude and durability (more efficient after longer ZIKV pre-exposure) of the immune response. Furthermore, our data suggest that the elicited immune modulation between both ZIKV-immune groups after DENV infection are more influenced by the time elapsed between ZIKV and DENV infections and the maturation of the cross-reactive immune memory, rather than a possible effect due to ZIKV strain variation. Collectively, our findings provide evidence of a non-detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.