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.

谓词SBIR/STTR I阶段赠款和团队的执行摘要 Tengen Biomedical Co.和Howard University获得了STTR I期赠款（5R41AI129119-02）美国国家过敏和传染病研究所（NIAID）于2017年。我们谓语的总体目标 STTR I期赠款是基于新颖的概念，开发出一种安全，有效且负担得起的Zika疫苗第三代黄素疫苗。 Zika病毒（ZIKV）发作和ZIKV感染与 Guillain -Barré综合征和先天性疾病（包括小头畸形）领导了世界健康组织在2016年宣布ZIKV为“国际公共卫生紧急关注”。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。为zikv的亚基因组复制品的构建， 2。稳定包装细胞系的发展，在反式中提供ZIKV结构蛋白C。 3。从受感染的包装细胞系中收获ZIKV PIV并分析包装单元的稳定性线路和PIV期间， 4。对小鼠提出的疫苗的安全性和免疫原性的初步分析。在过去的两年中，我们已经取得了8项重大成就，具体目的是： 1。野生型和突变寨卡病毒的传染性cDNA克隆的产生 2。通过选择性适应的稳定脊椎动物特异性复制的发展ZIKV 3。在脊椎动物细胞-ZIKV（VSRD-ZIKV）中稳定复制缺陷的DNA测序和分析新工程突变 4。在新生儿和3周大的免疫功能低下的小鼠中对VSRD-ZIKV的初步评估 5。Prime-Boost VSRD-ZIKV疫苗接种为防止致命的ZIKV挑战提供了强有力的保护免疫功能低下的小鼠 6。使用VSRD-ZIKV疫苗接种与ZIKV特异性的体液免疫和CD8 +IFN- +有关回答 7。VSRD-ZIKV提供保护并防止在受到挑战的雄性小鼠测试中的病毒积累与致命的zikv 8。使用VSRD-ZIKV免疫可防止受到质疑的怀孕小鼠的垂直传播致命的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 TC，Pang X.脊椎动物特异性复制缺陷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。在线印刷。 PMID：33075709 我们提出了I-Corps团队包括三名高素质的主要调查员。克里斯·D·塔（Chris D. Ta），MBA。首席执行官 Tengen Biomedical Co.和他在工业发展方面拥有超过17年的经验；小pang，博士STTR I期项目的首席研究员，他一直在推动该项目；和医学博士新生Gu。博士Tengen Biomedical Co.和STTR I期项目的共同创始人的共同创始人。 Gu博士一直是领导有远见的团队。这三个成员都致力于满足程序。