Development of a ZIKA viral pseudoinfectious virus as ZIKA vaccine candidate (STTR Phase II)

寨卡病毒伪传染性病毒作为寨卡病毒候选疫苗的研究进展 (第二阶段) 摘要 寨卡病毒流行和寨卡病毒感染与格林-巴利综合征的关系，以及 包括小头畸形在内的先天性残疾导致世界卫生组织宣布 ZIKV被评为2016年度国际关注的突发公共卫生事件。从那时起，各种ZIKV 已经开发了疫苗平台来控制未来的流行病。从历史上看，活体衰减 病毒疫苗产生持久的保护性免疫，但安全性降低，而灭活疫苗 疫苗提供高水平的初始保护，但显示出较弱的长期免疫力。第三 代囊缺陷黄病毒疫苗显示出令人惊讶的效力 在动物模型中具有很高的安全性。然而，它们需要复杂的包装系统或 辅助病毒复制，这使得获得许可的商业生产变得困难和昂贵。 最近，我们将双主机ZIKV转换为脊椎动物特有的复制缺陷 ZIKV(VSRD-ZIKV；wan等人在印刷中)，可以在相对较低的成本下高效生产 成本。在我们的第一阶段研究中，我们研究了VSRD-ZIKV在小鼠身上的安全性和有效性 模特。在拟议的第二阶段研究中，我们建议：1)研究遗传型和表型 VSRD-ZIKV在生产细胞基质上培养的稳定性2)种子批次的研制 3)在非人灵长类动物模型中评价VSRD-ZIKV的安全性和有效性。通过 完成这些目标，我们希望生产出一种具有高安全性和免疫原性的疫苗 可以转移到人体临床试验的个人资料。为了实现这些目标，我们有 建立了一支经验丰富的团队。霍华德大学与 腾根。此外，这两个小组将与Bioqual Inc.的专家密切合作，后者将 进行NHP试验。

Development of Zika viral pseudoinfectious virus as zika vaccine candidate (Phase 2) Abstract Zika virus epidemics and the association of ZIKV infection with Guillain–Barré syndrome, and congenital disabilities, including microcephaly, led the World Health Organization to declare ZIKV a “Public Health Emergency of International Concern” in 2016. Since then, various ZIKV vaccine platforms have been developed to control future epidemics. Historically, live-attenuated viral vaccines induce long-lasting protective immunity but reduced safety, whereas inactivated vaccines provide a high level of initial protection but exhibit weak long-term immunity. Third generation encapsidation-defective flavivirus vaccines have demonstrated surprisingly potent with high level of safety in animal models. However, they need complicated packaging systemor helper viral replicons, which make a licenced commercial production difficult and costly. Recently, we have converted a dual-host ZIKV into a vertebrate-specific replication defective ZIKV (VSRD-ZIKV; Wan et al in press) which can be efficiently produced at relatively low cost. In our phase 1 studies, we characterized the safety and efficacy of VSRD-ZIKV in a murine model. In the proposed phase 2 studies, we propose to: 1) study the genotypic and phenotypic stability of VSRD-ZIKV during culturing on manufacture cell substrate; 2) develop a seed lot stock; 3) evaluate the safety and efficacy of VSRD-ZIKV in a non-human primate model. By completing these goals we hope to produce a vaccine with a high safety and immunogenicity profile that could be moved toward human clinical trials. To achieve these goals we have established an experienced team. A strong partnership exists between the Howard University and Tengen. In addition, both groups will work closely with experts in Bioqual Inc who will be conducting the NHP trial.