Pre-existing immunity to flaviviruses can influence the outcome of subsequent
flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent
ZIKV infection and the protective efficacy of ZIKV
vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on
ZIKV infection and the protective efficacy of an inactivated ZIKV
vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV
vaccine developed
neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced
ZIKV infection and showed no overall reduction in ZIKV
vaccine protection. Moreover, passive transfer of purified DENV-specific
IgG from convalescent human donors did not augment
ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance
ZIKV infection or impair the protective efficacy of candidate ZIKV
vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.