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.