Time elapsed between Zika and dengue virus type 2 infections alters the magnitude of antibody and T cell responses but not viremia 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 increases the magnitude of the antibody and cell-mediated immune responses against DENV and that the different time intervals between infections alter the magnitude and durability of such responses (more after longer ZIKV pre-exposure). 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, we found no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection regardless the period of time between infections tested on this work. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.