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.

最近爆​​发的寨卡病毒（ZIKV）感染以及与成人Guillain-Barré综合征和先天性异常的潜在关联凸显了一种有效疫苗的紧迫性。ZIKV包膜糖蛋白（E _ZIKV）是病毒表面上最丰富的蛋白，在临床试验中已与病毒衣壳的膜前蛋白（prM）一起作为候选疫苗进行了评估。在这项研究中，我们对不同的基于E _ZIKV的候选疫苗在小鼠中诱导的免疫反应进行了正面对比。我们比较了不同的平台（DNA，重组蛋白），佐剂（聚（I：C），CpG ODN 1826）和免疫策略（同源，异源）。

佐剂效价的层次结构表明，聚（I：C）比CpG ODN更好。虽然在两次剂量后，聚（I：C）辅助免疫的抗体效价达到了平稳，但CpG ODN组需要额外的免疫剂量。此外，与CpG ODN相比，施用聚（I：C）诱导更高的E _ZIKV特异性细胞免疫应答。我们还显示，与同源_DNA增强免疫的E _ZIKV蛋白+聚（I：C）方案相比，同源DNA（pVAX-E _ZIKV）或异源方案（DNA /蛋白或蛋白/ DNA）免疫诱导的体液应答更为强劲。对细胞免疫反应的详细分析显示，同源（E _ZIKV  + poly（I：C））和异源（pVAX-E _ZIKV / E_ZIKV  +聚（I：C））_初免-加强疗法诱导了IFN-γ分泌细胞和产生细胞因子的CD4 ⁺ T细胞的最大量。

总体而言，我们的数据表明，与考虑同源DNA的其他策略（pVAX-E _ZIKV）相比，同源E _ZIKV  +聚（I：C）_初免-加强免疫足以诱导更强大的特异性E _ZIKV体液和细胞免疫应答。异源（pVAX-E _ZIKV / E _ZIKV  + poly（I：C），反之亦然）免疫。