Background: Zika virus (ZIKV) is a mosquito-borne flavivirus classified in Flaviviridae family such as dengue (DENV), yellow fever, and West Nile virus. An outbreak of ZIKV infection can pose a major public health risk because the contagion is unpredictable and induces severe pathology such as Guillan-Barre syndrome and neonatal microcephaly. However, an authorized ZIKV vaccine is not yet available, while several vaccine candidates are under development.Methods: In this study, we constructed a recombinant ZIKV vaccine (Z_EDIII) that includes ZIKV envelope protein domain III using E. coli expression system. Then both humoral and cellular immunity were examined in C57BL/6 (female, 8-weeks-old) mice via Indirect ELISA assay, PRNT, ELISpot and cytokine detection for IFN-γ, TNF-α, and IL-12. In addition, the cross protection against DENV was evaluated in pups from Z_EDIII vaccinated and infected dam.Results: Mice immunized by Z_EDIII produced a significant amount of ZIKV EDIII-specific and neutralizing antibodies. Together with antibodies, effector cytokines, such as IFN-γ, TNF-α, and IL-12 were induced. Moreover, vaccinated females delivered the adaptive immunity to neonates who are protective against ZIKV and DENV challenge.Conclusions: This study observed Z-EDIII-induced humoral and cellular immunity that protected hosts from both ZIKV and DENV challenges. The result suggests that our ZIKV EDIII recombinant vaccine has potential to provide a new preventive strategy against ZIKV infection.