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）

基本信息

批准号：
10259140
负责人：
XIAOWU PANG
金额：
$ 100万
依托单位：
TENGEN BIOMEDICAL CO.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10259140
关键词：
Animal Model Animals Area Attenuated Cells Clinic Clinical Trials Dengue Virus Development Dose Ensure Epidemic Exhibits Flavivirus Foundations Future Generations Genetic Genotype Goals Guillain Barré Syndrome Human Immune response Immunity Immunization Inactivated Vaccines Inherited Insecta International Macaca mulatta Microcephaly Modeling Mus Phase Phenotype Preparation Process Production Property Recombinants Replicon Reproducibility Research Personnel Safety Scheme Secondary Immunization Secure Seeds Small Business Technology Transfer Research Subunit Vaccines System Testing Therapeutic Time Universities Vaccine Production Vaccines Viral Viral Vaccines Viremia Virus Work World Health Organization ZIKA ZIKV infection Zika Virus Zika virus vaccine base commercial application cost cost efficient disability experience experimental study immunogenic immunogenicity in vivo lot production mouse model nonhuman primate novel pathogen phase 1 study phase 2 study preclinical evaluation public health emergency scale up vaccine candidate virus culture

项目摘要

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.

开发寨卡病毒假感染病毒作为寨卡候选疫苗（第二阶段）抽象的寨卡病毒流行以及寨卡病毒感染与格林-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在2016年被列为“国际关注的突发公共卫生事件”。此后，各种ZIKV 疫苗平台的开发是为了控制未来的流行病，从历史上看，是减毒活疫苗。病毒疫苗可诱导持久的保护性免疫力，但安全性降低，而灭活疫苗则疫苗提供高水平的初始保护，但长期免疫力较弱。一代衣壳缺陷型黄病毒疫苗已被证明具有惊人的效力在动物模型中具有高水平的安全性，但它们需要复杂的包装系统或。辅助病毒复制子，这使得获得许可的商业生产变得困难且成本高昂。最近，我们将双宿主 ZIKV 转化为脊椎动物特异性复制缺陷病毒 ZIKV（VSRD-ZIKV；Wan 等人正在出版），可以在相对较低的成本下高效生产在我们的第一阶段研究中，我们表征了 VSRD-ZIKV 在小鼠中的安全性和有效性。在拟议的第二阶段研究中，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) 在非人类灵长类动物模型中评估 VSRD-ZIKV 的安全性和有效性。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为了实现这些目标，我们有可能将其用于人体临床试验。霍华德大学和霍华德大学之间建立了一支经验丰富的团队。此外，两个小组将与 Bioqual Inc 的专家密切合作。进行 NHP 试验。