Amaral Marcelo Pires, Apostolico Juliana de Souza, Tomita Nádia, Coirada Fernanda Caroline, Lunardelli Victória Alves Santos, Fernandes Edgar Ruz, Souza Higo Fernando Santos, Astray Renato Mancini, Boscardin Silvia Beatriz, Rosa Daniela Santoro
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil.
Vaccine. 2020 Apr 29;38(20):3653-3664. doi: 10.1016/j.vaccine.2020.03.037. Epub 2020 Apr 2.
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) 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-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-specific cellular immune responses than CpG ODN. We also show that immunization with homologous prime-boost E protein + poly (I:C) regimen induced a more robust humoral response than homologous DNA (pVAX-E) or heterologous regimens (DNA/protein or protein/DNA). A detailed analysis of cellular immune responses revealed that homologous (E + poly (I:C)) and heterologous (pVAX-E/E + 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 + poly (I:C) prime-boost immunization is sufficient to induce more robust specific-E humoral and cellular immune responses than the other strategies that contemplate homologous DNA (pVAX-E) or heterologous (pVAX-E/E + poly (I:C), and vice-versa) immunizations.
近期寨卡病毒（ZIKV）感染的爆发以及其与成人吉兰 - 巴雷综合征和先天性异常的潜在关联凸显了研发有效疫苗的紧迫性。寨卡病毒包膜糖蛋白（E）是病毒表面最丰富的蛋白质，并且在临床试验中已与病毒衣壳的前膜蛋白（prM）一起作为候选疫苗进行了评估。在本研究中，我们对不同基于E的候选疫苗在小鼠中诱导的免疫反应进行了直接比较。我们比较了不同的平台（DNA、重组蛋白）、佐剂（聚肌胞苷酸（poly (I:C)）、CpG寡脱氧核苷酸1826）和免疫策略（同源、异源）。佐剂效力的层级显示聚肌胞苷酸是比CpG寡脱氧核苷酸更优的佐剂。虽然聚肌胞苷酸辅助免疫在两剂后抗体滴度达到平台期，但CpG寡脱氧核苷酸组需要额外一剂免疫。此外，聚肌胞苷酸的给药诱导的E特异性细胞免疫反应高于CpG寡脱氧核苷酸。我们还表明，同源初免 - 加强E蛋白 + 聚肌胞苷酸方案诱导的体液反应比同源DNA（pVAX - E）或异源方案（DNA/蛋白或蛋白/DNA）更强。对细胞免疫反应的详细分析表明，同源（E + 聚肌胞苷酸）和异源（pVAX - E/E + 聚肌胞苷酸）初免 - 加强方案诱导的分泌IFN - γ的细胞和产生细胞因子的CD4 T细胞数量最多。总体而言，我们的数据表明，与考虑同源DNA（pVAX - E）或异源（pVAX - E/E + 聚肌胞苷酸，反之亦然）免疫的其他策略相比，同源E + 聚肌胞苷酸初免 - 加强免疫足以诱导更强的特异性E体液和细胞免疫反应。
