Research Project 1: Vaccine for Rapid Response to Filovirus Outbreak

研究项目1：快速应对丝状病毒爆发的疫苗

• 批准号: 10576279
• 负责人: Stefan L Hamm
• 金额: $ 76.18万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-08 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576279
• 关键词: Research; Project; Vaccine; Rapid; Response

PROJECT SUMMARY/ABSTRACT – Research Project 1 Ebola virus (EBOV) and Marburg virus (MARV) are filamentous enveloped non-segmented negative sense RNA viruses representing the two genera that comprise the family Filoviridae. The Marburgvirus genus contains one species (MARV), while the Ebolavirus genus is comprised of five recognized species: Sudan ebolavirus (SUDV), Zaire ebolavirus (EBOV), Tai Forest ebolavirus (TAFV), Reston ebolavirus (RESTV), and Bundibugyo ebolavirus (BDBV). These viruses are important human pathogens with case fatality rates ranging from 70% to 90% for EBOV, up to 90% for MARV, approximately 55% for SUDV, and 25-50% for BDBV. These agents are classified as Category A Priority Pathogens by the NIAID/NIH and CDC, and there are presently no licensed active or passive interventions for exposure resulting from natural outbreak, laboratory accident, or deliberate misuse. The public health concern is based on both the emerging infectious disease status of these viruses and their potential use as biologic weapons. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks in endemic areas of sub-Saharan Africa, with laboratory workers engaged in filovirus research, and with military and civilian personnel threatened by weaponized filoviruses. The ideal vaccine to meet both the outbreak and bioweapon scenarios would rapidly confer protection against all species of EBOV and MARV with a single dose. Among the vaccine strategies tested for single dose protection, the most successful have been vectored vaccines based on vesicular stomatitis virus (VSV). The progressing urbanization of sub-Saharan Africa has increased the probability that a filovirus infected individual will enter an area of high population density either unknowingly or to seek medical aid. As seen in the recent west African outbreak, the increased mobility within and between the urban centers can rapidly expand the number and geographic distribution of cases. Thus, in the absence of widespread prophylactic immunization, the most effective uses of a vaccine against the filoviruses will be protection of healthcare workers and breaking spread using ‘ring vaccination’. The first application is aided by, and the second application is dependent upon, a rapid onset of protection. Funded work under NIAID contract HHSN272201700077C supports development of vaccines for EBOV, SUDV, and MARV that are vectored with rVSVN4CT1, a live attenuated VSV vector that has proven safe in multiple clinical trials. This application proposes to develop an rVSVN4CT1-vectored BDBV vaccine through MVS production and IND-enabling toxicology testing, to establish the time to onset of protection provided by rVSVN4CT1-vectored vaccines against the four filovirus species of greatest concern (EBOV, SUDV, BDBV, and MARV). In addition, it proposes to address the questions regarding the vaccine valency providing the most effective formulation for use in a rapid response setting.

项目摘要/摘要 - 研究项目1 埃博拉病毒（EBOV）和马堡病毒（MARV）是丝状包裹的非细分负性RNA 代表包括家族的两个属的病毒。马堡病毒属包含一个 物种（MARV），而埃博拉病毒属由五种公认物种组成：苏丹埃博拉病毒（SUDV），，，， Zaire Ebolavirus（EBOV），TAI Forest Ebolavirus（TAFV），Reston Ebolavirus（RESTV）和Bundibugyo Ebolavirus （BDBV）。这些病毒是重要的人类病原体，病例死亡率范围从70％到90％ EBOV，MARV最高90％，SUDV约为55％，而BDBV最高为25-50％。这些代理被分类 作为NIAID/NIH和CDC的优先病原体类别，没有授权的活动或 自然爆发，实验室事故或故意滥用导致暴露的被动干预措施。 公共卫生问题是基于这些病毒的新兴疾病状况及其 潜在用作生物武器。有效的预防性疫苗会发现医疗应用 在撒哈拉以南非洲地区流行地区爆发期间的人员和密切联系，与实验室工人 从事FILOVIRUS研究，并受到武器化的污物病毒威胁的军事和平民。 理想的疫苗可以满足爆发和生物武器场景 EBOV和MARV的物种，单剂量。在测试单剂量保护的疫苗策略中， 最成功的是基于囊泡口腔炎病毒（VSV）的vecte疫苗。进展 撒哈拉以南非洲的城市化增加了丝状病毒感染者将进入的可能性 人口密度高的地区要么未知或寻求医疗援助。如最近的西非 爆发，城市中心内部和之间的流动性增加可以迅速扩大数量，并且 案件的地理分布。在没有宽度预防性免疫的情况下，最多 疫苗针对铁病毒的有效用途将是保护医疗工人和破坏差异 使用“环疫苗接种”。第一个应用程序是由第二个应用程序的，第二个应用程序取决于快速 保护发作。根据NIAID合同HHSN272201700077C的资助工作支持开发 EBOV，SUDV和MARV的疫苗与RVSVN4CT1进行载体，这是一种活的衰减VSV矢量的疫苗 在多个临床试验中被证明是安全的。此申请提案要开发RVSVN4CT1向量的BDBV 通过MVS生产和成分毒理学测试进行疫苗，以确定发芽的时间 由RVSVN4CT1向量的疫苗提供针对四种最引起关注的丝状病毒的疫苗（Ebov，Sudv， BDBV和MARV）。此外，它提议解决有关疫苗价值的问题 在快速响应设置中使用的最有效的公式。