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

开发 ZIKA 病毒假感染病毒作为 ZIKA 候选疫苗（STTR II 期）

• 批准号: 10612753
• 负责人: XIAOWU PANG
• 金额: $ 100万
• 依托单位: TENGEN BIOMEDICAL CO.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612753
• 关键词: Acceleration; Animal Model; Animals; Area; Attenuated; Cells; Clinic; Clinical Trials; Dengue Virus; Development; Dose; Ensure; Epidemic; Exhibits; Flavivirus; Foundations; Generations; Genetic; Genotype; Goals; Guillain Barré Syndrome; Human; Immune response; Immunity; Immunization; Inactivated Vaccines; Inherited; Insecta; International; Licensing; Macaca mulatta; Microcephaly; Modeling; Mus; Phase; Phenotype; Preparation; Process; Production; Property; Recombinants; Replicon; Reproducibility; Research Personnel; Safety; Scheme; Secondary Immunization; Secure; Small Business Technology Transfer Research; Subunit Vaccines; Testing; Therapeutic; Universities; Vaccine Production; Vaccines; Viral; Viral Vaccines; Viremia; Virus; Work; World Health Organization; ZIKA; ZIKV infection; Zika Virus; Zika virus vaccine; commercial application; cost; cost efficient; disability; epidemic virus; experience; experimental study; future epidemic; immunogenic; immunogenicity; in vivo; lot production; manufacture; manufacturing scale-up; mouse model; nonhuman primate; novel; pathogen; phase 1 study; phase 2 study; preclinical evaluation; public health emergency; vaccine candidate; vaccine platform

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.

寨卡病毒假感染病毒作为寨卡候选疫苗的开发 （第二阶段） 摘要 寨卡病毒流行以及ZIKV感染与格林-巴利综合征的关联，以及 先天性残疾，包括小头畸形，导致世界卫生组织宣布， ZIKV于2016年被列为“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，减毒活疫苗 病毒疫苗诱导持久的保护性免疫，但安全性降低，而灭活疫苗 疫苗提供高水平的初始保护，但表现出较弱的长期免疫力。三 第二代减毒缺陷型黄病毒疫苗已显示出惊人的效力 在动物模型中安全性高。然而，它们需要复杂的包装系统， 辅助病毒复制子，这使得获得许可的商业生产变得困难和昂贵。 最近，我们已经将双宿主ZIKV转化为脊椎动物特异性复制缺陷型ZIKV。 ZIKV（VSRD-ZIKV; Wan等，出版中），其可以在相对低的温度下有效地生产。 成本在我们的1期研究中，我们表征了VSRD-ZIKV在小鼠中的安全性和有效性。 模型在拟定的II期研究中，我们建议：1）研究基因型和表型 VSRD-ZIKV在制造细胞基质上培养期间的稳定性; 2）开发种子批次 3）评估VSRD-ZIKV在非人灵长类动物模型中的安全性和功效。通过 完成这些目标，我们希望生产出具有高安全性和免疫原性的疫苗。 可以用于人类临床试验的概况。为了实现这些目标，我们 建立了一支经验丰富的团队。霍华德大学与 天元此外，这两个小组将与Bioqual Inc的专家密切合作， 进行NHP试验。