ZIKV-envelope proteins induce specific humoral and cellular immunity in distinct mice strains

Recent outbreaks of Zika virus (ZIKV) infection have highlighted the need for a better understanding of ZIKV-specific immune responses. The ZIKV envelope glycoprotein (E_ZIKV) is the most abundant protein on the virus surface and it is the main target of the protective immune response. E_ZIKV protein contains the central domain (EDI), a dimerization domain containing the fusion peptide (EDII), and a domain that binds to the cell surface receptor (EDIII). In this study, we performed a systematic comparison of the specific immune response induced by different E_ZIKV recombinant proteins (E_ZIKV, EDI/II_ZIKV or EDIII_ZIKV) in two mice strains. Immunization induced high titers of E-specific antibodies which recognized ZIKV-infected cells and neutralized the virus. Furthermore, immunization with E_ZIKV, EDI/II_ZIKV and EDIII_ZIKV proteins induced specific IFNγ-producing cells and polyfunctional CD4⁺ and CD8⁺ T cells. Finally, we identified 4 peptides present in the envelope protein (E_1-20, E_51-70, E_351-370 and E_361-380), capable of inducing a cellular immune response to the H-2K^d and H-2K^b haplotypes. In summary, our work provides a detailed assessment of the immune responses induced after immunization with different regions of the ZIKV envelope protein.