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

基本信息

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
项目类别：
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

项目摘要

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.

Predicate SBIR/STTR 第一阶段资助和团队的执行摘要 TenGen Biomedical Co. 和霍华德大学获得 STTR 第一阶段资助 (5R41AI129119-02) 国家过敏和传染病研究所 (NIAID)，2017 年。我们谓词的总体目标 STTR 第一阶段资助是基于新概念开发一种安全、有效且负担得起的寨卡疫苗第三代黄病毒疫苗。寨卡病毒 (ZIKV) 流行以及 ZIKV 感染与疾病的关联。格林-巴利综合征和先天性残疾，包括小头畸形，引领了世界卫生组织于 2016 年宣布 ZIKV 为“国际关注的突发公共卫生事件”。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.开发提供反式ZIKV结构蛋白C的稳定包装细胞系。 3. 从受感染的包装细胞系中收获 ZIKV PIV 并分析包装细胞的稳定性通道中的线路和 PIV， 4. 初步分析所提出的疫苗在小鼠中的安全性和免疫原性。两年来，我们围绕具体目标，取得了8项重大成果： 1. 野生型和突变寨卡病毒感染性 cDNA 克隆的生成 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 周龄免疫受损小鼠中的初步评估 5. 初免加强 VSRD-ZIKV 疫苗接种可针对致命的 ZIKV 挑战提供强有力的保护免疫功能低下的小鼠 6. VSRD-ZIKV 疫苗接种与 ZIKV 特异性体液免疫和 CD8+IFN- + 相关回应 7. VSRD-ZIKV 在受攻击的雄性小鼠测试中提供保护并防止病毒积累携带致命的寨卡病毒 8. VSRD-ZIKV 免疫可防止受 ZIKV 攻击的怀孕小鼠的垂直传播致命寨卡病毒此外，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 TC，Pang X。脊椎动物特异性复制缺陷型寨卡病毒的生成和初步表征。病毒学。2020 年 10 月 6 日；doi：10.1016/j.virol。印刷前在线：33075709。我们建议 I-Corps 团队包括三名高素质的关键调查员，他是 MBA 的首席执行官。天正生物医药有限公司拥有超过十七年的行业开发经验； STTR一期项目首席研究员，博士，顾新斌，医学博士。天元生物医药联合创始人、STTR一期项目联合研究员，博士。领导团队中的所有三名成员都致力于满足团队的时间要求。程序。