Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Rep. 2019 Sep 3;28(10):2634-2646.e4. doi: 10.1016/j.celrep.2019.08.005.
The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD8 T cell independent, and for GAd-Eecto requires the complement component C1q. Immunization of GAd-Zvp induces antibodies against a key neutralizing epitope on domain III of E protein and confers durable protection as evidenced by memory B and long-lived plasma cell responses and challenge studies 9 months later. In two models of ZIKV infection during pregnancy, GAd-Zvp prevents maternal-to-fetal transmission. The gorilla adenovirus-based vaccine platform encoding full-length prM and E genes is a promising candidate for preventing congenital ZIKV syndrome and possibly infection by other flaviviruses.
寨卡病毒（ZIKV）的致畸潜力使得开发有效的疫苗成为全球卫生的当务之急。在这里，我们生成了两种基于大猩猩腺病毒的寨卡病毒疫苗，它们分别编码前膜（prM）和包膜（E）蛋白（GAd-Zvp）或 prM 和 E 蛋白的胞外结构域（GAd-Eecto）。这两种疫苗都能诱导体液和细胞免疫反应，并能预防小鼠感染寨卡病毒后的致死性。保护作用依赖于抗体，与 CD8 T 细胞无关，而 GAd-Eecto 需要补体成分 C1q。GAd-Zvp 免疫可诱导针对 E 蛋白结构域 III 上关键中和表位的抗体，并在 9 个月后的记忆 B 和长寿浆细胞反应和挑战研究中提供持久的保护。在妊娠期间的两种寨卡病毒感染模型中，GAd-Zvp 可预防母婴传播。编码全长 prM 和 E 基因的基于大猩猩腺病毒的疫苗平台是预防先天性寨卡病毒综合征和可能感染其他黄病毒的有前途的候选物。
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