Homologous prime-boost with Zika virus envelope protein and poly (I:C) induces robust specific humoral and cellular immune responses

The recent outbreaks of Zika virus (ZIKV) infection and the potential association with Guillain-Barré syndrome in adults and with congenital abnormalities have highlighted the urgency for an effective vaccine. The ZIKV Envelope glycoprotein (E_ZIKV) is the most abundant protein on the virus surface, and has been evaluated together with the pre-membrane protein (prM) of the viral coat as a vaccine candidate in clinical trials. In this study, we performed a head-to-head comparison of the immune response induced by different E_ZIKV-based vaccine candidates in mice. We compared different platforms (DNA, recombinant protein), adjuvants (poly (I:C), CpG ODN 1826) and immunization strategies (homologous, heterologous).The hierarchy of adjuvant potency showed that poly (I:C) was a superior adjuvant than CpG ODN. While poly (I:C) assisted immunization reached a plateau in antibody titers after two doses, the CpG ODN group required an extra immunization dose. Besides, the administration of poly (I:C) induced higher E_ZIKV-specific cellular immune responses than CpG ODN. We also show that immunization with homologous prime-boost E_ZIKV protein + poly (I:C) regimen induced a more robust humoral response than homologous DNA (pVAX-E_ZIKV) or heterologous regimens (DNA/protein or protein/DNA). A detailed analysis of cellular immune responses revealed that homologous (E_ZIKV + poly (I:C)) and heterologous (pVAX-E_ZIKV/E_ZIKV + poly (I:C)) prime-boost regimens induced the highest magnitude of IFN-γ secreting cells and cytokine-producing CD4⁺ T cells.Overall, our data demonstrate that homologous E_ZIKV + poly (I:C) prime-boost immunization is sufficient to induce more robust specific-E_ZIKV humoral and cellular immune responses than the other strategies that contemplate homologous DNA (pVAX-E_ZIKV) or heterologous (pVAX-E_ZIKV/E_ZIKV + poly (I:C), and vice-versa) immunizations.