rVSV Vectored Vaccine to Protect Against Ebola and Marburg Viruses

rVSV 载体疫苗可预防埃博拉病毒和马尔堡病毒

• 批准号: 8653530
• 负责人: John Hayward Eldridge
• 金额: $ 93.74万
• 依托单位: PROFECTUS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653530
• 关键词: Africa South of the Sahara; Area; Attenuated; Case Fatality Rates; Categories; Centers for Disease Control and Prevention (U.S.); Characteristics; Cyclic GMP; Democratic Republic of the Congo; Development; Disease Outbreaks; Drug Formulations; Ebola virus; Effectiveness; Emerging Communicable Diseases; Exposure to; Family; Filoviridae; Filovirus; Frankfurt-Marburg Syndrome Virus; Future; GTP-Binding Proteins; Glycoproteins; Health Personnel; Human; Human Resources; Infection; Intervention; Ivory Coast; Laboratories; Life; Military Personnel; Monkeys; National Institute of Allergy and Infectious Disease; Principal Investigator; Public Health; RNA Viruses; Recombinants; Research; Reston; Safety; Seeds; Sudan; Technology; Testing; Toxicology; United States National Institutes of Health; Vaccines; Vesicular stomatitis Indiana virus; Virus; base; immunogenicity; laboratory accident; meetings; neurovirulence; nonhuman primate; pathogen; programs; prophylactic; vaccine delivery; vector; weapons

DESCRIPTION (provided by applicant): 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. These viruses are important human pathogens with case fatality rates ranging from 55% to 90% for EboV and up to 90% for MarV. These agents are classified as Category A Priority Pathogens by the NIAID/NIH and CDC, and there are presently no approved active or passive interventions for exposure resulting from natural outbreak, laboratory accident, or deliberate misuse. 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 bio-weapon scenarios would rapidly confer protection against all species of EboV and MarV with a single administration. Among the vaccine technologies investigated to date, a tri-valent filovirus vaccine vectored by recombinant vesicular stomatitis virus (rVSV) has shown the greatest potential as a single administration vaccine with the capacity to rapidly provide broad protection against EboV and MarV. Profectus BioSciences has developed a replication competent attenuated rVSV vaccine delivery platform (rVSVN4CT1) that: 1) retains the immunogenicity of vaccines based on the non-attenuated vector, 2) has been manufactured under cGMPs at commercial scale, and 3) has been judged by the FDA to be safe for human testing. Thus, this application proposes: 1) to confirm that an attenuated tri-valent rVSVN4CT1 vectored filovirus vaccine will protect monkeys against challenge with EboV and MarV, 2) compliantly prepare seed stocks of the three viruses in the vaccine under conditions that will support future manufacture under cGMPs, 3) use the compliant seed stocks to prepare tri-valent vaccine that will be tested in a GLP neuro-toxicology study in non-human primates to confirm safety, 4) use the compliant tri-valent vaccine in development studies to identify a lyophilized formulation with the stability characteristics required for practical field use, and 5) test the lyophilized tri-valent vaccine to confirm that it protects NHPs from EboV and MarV when administered pre-exposure and post-exposure.

描述（由申请人提供）：埃博拉病毒（EBOV）和MARBURG病毒（MARV）是丝状包围的非细分负性RNA病毒，代表组成家族的两个属属。这些病毒是重要的人类病原体，病例死亡率范围从55％到90％，而MARV的死亡率范围为90％。这些药物被NIAID/NIH和CDC归类为A类病原体，目前尚无自然爆发，实验室事故或故意滥用的批准的主动或被动干预措施。公共卫生的关注是基于这些病毒的新兴传染病状况及其作为生物武器的潜在用途。一种有效的预防性疫苗将在撒哈拉以南非洲地区的特有地区的爆发期间与医务人员和密切联系，并进行实验室工人从事filevirus研究，并与受武器化的污物病毒威胁的军事和平民人员。符合爆发和生物武器场景的理想疫苗将通过单个管理迅速允许对EBOV和MARV的所有物种进行保护。在迄今为止研究的疫苗技术中，由重组囊泡口腔炎病毒（RVSV）介绍的三值丝病毒疫苗显示出最大的潜力，作为单个给药疫苗，具有快速提供对EBOV和MARV的广泛保护的能力。 Profectus Biosciences已开发了一种有能力减弱的RVSV疫苗输送平台（RVSVN4CT1）的复制，即：1）保留基于未衰减载体的疫苗的免疫原性，2）已在CGMPS下以商业规模制造，以及3）受到FDA的判断。因此，该申请提出：1）确认，衰减的三价RVSVN4CT1矢量疫苗疫苗将保护猴子免受Ebov and Marv的挑战，2）在疫苗中，三种病毒的种子库存在疫苗中的三种种子库存在条件下将在CGMPS下进行造成的疫苗，3）在cgmps下，3）将在cgmps下进行处理，3）非人类灵长类动物的神经毒理学研究以确认安全性，4）使用在开发研究中使用兼容的三价疫苗来鉴定具有实用现场使用所需的稳定性特征的冻干配方； 5）测试冻干的三价疫苗来确认它的确认 当受到暴露前和暴露后施用时，保护NHP免受EBOV和MARV。