Development of Zika viral pseudoinfectious virus as Zika vaccine candidate

开发寨卡病毒假感染病毒作为寨卡候选疫苗

• 批准号: 10304384
• 负责人: XIAOWU PANG
• 金额: $ 5.2万
• 依托单位: TENGEN BIOMEDICAL CO.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-17 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304384
• 关键词: Achievement; Automobile Driving; CD8B1 gene; Cell Line; Cells; Complementary DNA; DNA sequencing; Defect; Development; Doctor of Philosophy; Engineering; Epidemic; Evaluation; Flavivirus; Generations; Grant; Guillain Barré Syndrome; Harvest; Humoral Immunities; Immunization; Immunocompromised Host; Industry; Innovation Corps; Interferons; International; Laboratories; Microcephaly; Mus; Mutation; National Institute of Allergy and Infectious Disease; Newborn Infant; Paper; Phase; Principal Investigator; Protein C; Publishing; Replicon; Research Personnel; Safety; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Structural Protein; Testis; Time; United States National Institutes of Health; Universities; Vaccination; Vaccines; Vertical Disease Transmission; Viral; Virus; World Health Organization; ZIKA; ZIKV infection; Zika Virus; Zika virus vaccine; base; disability; experience; immunogenicity; male; member; mutant; novel; pregnant; prevent; programs; public health emergency; response; vaccine candidate; virology

Executive Summary of Predicate SBIR/STTR Phase I Grant and Team TenGen Biomedical Co. and Howard University received an STTR Phase I grant (5R41AI129119-02) from the National Institute of Allergy and Infectious Diseases (NIAID) in 2017. The overall objective of our predicate STTR Phase I grant is to develop a safe, effective, and affordable Zika vaccine based on the novel concept of the third generation of flavivirus vaccine. Zika virus (ZIKV) 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. Therefore, an effective Zika vaccine is urgently needed. The project proposed four specific aims: 1. Construction of subgenomic replicon for ZIKV, 2. Development of stable packaging cell lines providing ZIKV structural protein C in trans. 3. Harvest of ZIKV PIVs from infected packaging cell line and analyzing the stability of the packaging cell lines and PIV during passages, 4. Preliminary analysis of the safety and immunogenicity of the proposed vaccine in mice. In the past two years, we have made 8 significant achievements forward the specific aims: 1. Generation of Infectious cDNA Clones of Wildtype and Mutant Zika Virus 2. Development of stable Vertebrate Specific Replication Defected ZIKV by selective adaptation 3. DNA sequencing of the stably replication-defective in vertebrate cells-ZIKV (VSRD-ZIKV) and analysis of new engineered mutations 4. Preliminary evaluation of VSRD-ZIKV in both newborn and 3-week-old immunocompromised mice 5. Prime-boost VSRD-ZIKV vaccination provides robust protection against lethal ZIKV challenge in immunocompromised mice 6. Vaccination with VSRD-ZIKV is associated with ZIKV-specific humoral immunity and CD8+IFN- + responses 7. VSRD-ZIKV provides protection and prevents viral accumulation in the testes of male mice challenged with lethal ZIKV 8. Immunization with VSRD-ZIKV protects against vertical transmission in pregnant mice challenged with lethal ZIKV In addition, we recently published a paper based on this study: Wan S, Cao S, Wang X, Zhou Y, Yan W, Gu X, Wu TC, Pang X. Generation and preliminary characterization of vertebrate-specific replication-defective Zika virus. Virology. 2020 Oct 6;552:73-82. doi: 10.1016/j.virol. 2020.09.001. Online ahead of print. PMID: 33075709 We proposed the I-Corps team included three highly qualified key investigators. Chris D. Ta, MBA. CEO of TenGen Biomedical Co. and he has over seventeen years of experience in industry development; Xiaowu Pang, Ph.D. Principal Investigator of the STTR Phase I project and he has been driving the project; and Xinbin Gu, MD. Ph.D. Co-founder of TenGen Biomedical Co. and Co-Investigator of the STTR Phase I project. Dr. Gu has been leading the visionary on the team. All three members are committed to the time requirements of the program.

同品种器械SBIR/STTR I期资助和团队的执行摘要 TenGen Biomedical Co.和霍华德大学获得了STTR第一阶段资助（5R41AI129119 - 02）， 国家过敏和传染病研究所（NIAID）于2017年。我们同品种器械的总体目标是 STTR第一阶段拨款是开发一种安全，有效，负担得起的寨卡疫苗，基于新的概念， 第三代黄病毒疫苗。寨卡病毒（ZIKV）流行病以及ZIKV感染与 格林-巴利综合征和先天性残疾，包括小头畸形，导致世界卫生组织 2016年，该组织宣布ZIKV为“国际关注的突发公共卫生事件”。所以一间 因此，迫切需要有效的寨卡疫苗。 该项目提出了四个具体目标： 1. ZIKV亚基因组复制子的构建， 2.提供反式ZIKV结构蛋白C的稳定包装细胞系的开发 3.从感染的包装细胞系收获ZIKV PIV并分析包装细胞的稳定性 通道期间的线和PIV， 4.初步分析拟议疫苗在小鼠中的安全性和免疫原性。 在过去的两年里，我们在具体目标方面取得了8项重大成就： 1.野生型和突变型寨卡病毒感染性cDNA克隆的产生 2.通过选择性适应开发稳定的脊椎动物特异性复制缺陷ZIKV 3.脊椎动物细胞中稳定复制缺陷型ZIKV（VSRD-ZIKV）的DNA测序和分析 新的工程突变 4. VSRD-ZIKV在新生和3周龄免疫功能低下小鼠中的初步评价 5.初免-加强VSRD-ZIKV疫苗接种提供了针对致死性ZIKV攻击的稳健保护， 免疫受损小鼠 6.用VSRD-ZIKV接种与ZIKV特异性体液免疫和CD8 + IFN-+相关 响应 7. VSRD-ZIKV提供保护并防止病毒在受攻击的雄性小鼠睾丸中积累 致命的ZIKV病毒 8.用VSRD-ZIKV进行免疫保护在用抗病毒药物攻击的妊娠小鼠中免受垂直传播。 致死ZIKV 此外，我们最近发表了一篇基于这项研究的论文：Wan S，Cao S，Wang X，Zhou Y，Yan W，Gu X，Wu 彭世辉脊椎动物特异性复制缺陷型寨卡病毒的产生和初步表征。 病毒学2020年10月6日; 552：73 - 82。doi：10.1016/j.virol. 2020.09.001.在印刷之前在线。PMID：33075709 我们建议I-Corps团队包括三名高素质的关键调查员。克里斯·D Ta，MBA。首席执行官 他拥有超过十七年的行业开发经验;庞晓武， 博士STTR第一阶段项目的首席研究员，他一直在推动该项目;以及Xinbin Gu，MD。 博士TenGen Biomedical Co.的联合创始人和STTR第一阶段项目的联合研究者。古医生一直在 带领团队中的梦想家。所有三名成员都致力于遵守《公约》的时间要求。 程序.