Dengue and Zika Virus Serological Cross-reactivity and their Impact on Pathogenesis in Mice.

Pre-existing immunity to Zika virus (ZIKV) or dengue virus (DENV) may alter the course of their infection and here we use robust mouse models to examine pathological outcomes following passive immunization, sequential cross-infection or vaccination with inactivated virus. DENV infection was enhanced (ADE) or suppressed by both DENV and ZIKV immunity. Notably inactivated ZIKV vaccination enhanced dengue disease severity, although it was highly protective against ZIKV infection. On the other hand, ADE was not observed upon ZIKV infection in mice that were passively immunized or pre-infected with DENV. Surprisingly, however, we found that vaccination with inactivated DENV enhanced ZIKV infection, mainly in the mesenteric lymph node, indicating the potential for DENV immunity to cause ADE in vivo. Collectively, our data calls for greater attention to detail in the design of ZIKV or DENV vaccines.