TCRb repertoire dynamics in the context of Zika vaccine

The epidemic spread of Zika virus (ZIKV), associated with devastating neurologic syndromes, has driven the development of multiple ZIKV vaccines candidates. An effective vaccine should induce ZIKV-specific T cell responses, which are shown to improve the establishment of humoral immunity and contribute to viral clearance. Here we investigated how previous immunization against Japanese encephalitis virus (JEV) and yellow fever virus (YFV) influences T cell responses elicited by a Zika purified-inactivated virus (ZPIV) vaccine. We demonstrate that three doses of ZPIV vaccine elicited robust CD4 T cell responses to ZIKV structural proteins, while ZIKV-specific CD4 T cells in pre-immunized individuals with JEV vaccine, but not YFV vaccine, were more durable and directed predominantly towards conserved epitopes, which elicited more Th1 and Th2 cytokine production. In addition, TCR repertoire analysis revealed preferential expansion of cross-reactive clonotypes between JEV and ZIKV. These findings suggest that pre-existing immunity against JEV may prime the establishment of stronger CD4 T cell responses to ZPIV vaccination.