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<sub>ZIKV</sub>) is the most abundant protein on the virus surface and it is the main target of the protective immune response. E<sub>ZIKV</sub> 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<sub>ZIKV</sub> recombinant proteins (E<sub>ZIKV</sub>, EDI/II<sub>ZIKV</sub> or EDIII<sub>ZIKV</sub>) 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<sub>ZIKV</sub>, EDI/II<sub>ZIKV</sub> and EDIII<sub>ZIKV</sub> proteins induced specific IFNγ-producing cells and polyfunctional CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Finally, we identified 4 peptides present in the envelope protein (E<sub>1-20</sub>, E<sub>51-70</sub>, E<sub>351-370</sub> and E<sub>361-380</sub>), capable of inducing a cellular immune response to the H-2K<sup>d</sup> and H-2K<sup>b</sup> haplotypes. In summary, our work provides a detailed assessment of the immune responses induced after immunization with different regions of the ZIKV envelope protein.
© 2022. The Author(s).