Limited flavivirus cross-reactive antibody responses elicited by a ZIKV DNA vaccine candidate in humans.

ZIKV DNA vaccine VRC5283 encoding viral structural genes, has been shown to be immunogenic in humans. Recognizing that antigenically-related flaviviruses co-circulate in regions with ZIKV activity, we explored the degree of antibody cross-reactivity elicited by this vaccine candidate using genetically-diverse flaviviruses. The antibody response of vaccinated individuals with no evidence of prior flavivirus infection or vaccine experience had a limited capacity to bind heterologous viruses. In contrast, vaccine-elicited antibodies from individuals with prior flavivirus experience had a greater capacity to bind, but not neutralize, distantly-related flaviviruses. These findings suggest that prior flavivirus exposure shapes the humoral immune response to vaccination.