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: 8837561
• 负责人: John Hayward Eldridge
• 金额: $ 94.72万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837561
• 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）和马尔堡病毒（MarV）是丝状包膜非节段负义RNA病毒，代表构成丝状病毒科的两个属。这些病毒是重要的人类病原体，EboV 的病死率在 55% 至 90% 之间，MarV 的病死率高达 90%。这些病原体被 NIAID/NIH 和 CDC 归类为 A 类优先病原体，目前还没有批准的主动或被动干预措施来应对自然爆发、实验室事故或故意滥用造成的暴露。公共卫生担忧是基于这些病毒新出现的传染病状况及其作为生物武器的潜在用途。有效的预防性疫苗将适用于撒哈拉以南非洲流行地区疫情爆发期间的医务人员和密切接触者、从事丝状病毒研究的实验室工作人员以及受到武器化丝状病毒威胁的军事和文职人员。满足爆发和生物武器场景的理想疫苗将通过单次给药快速提供针对所有种类的埃博拉病毒和马病毒的保护。在迄今为止研究的疫苗技术中，以重组水泡性口炎病毒（rVSV）为载体的三价丝状病毒疫苗显示出作为单次给药疫苗的最大潜力，能够快速提供针对埃博拉病毒和马病毒的广泛保护。 Profectus BioSciences 开发了一种具有复制能力的减毒 rVSV 疫苗递送平台 (rVSVN4CT1)，该平台：1) 保留基于非减毒载体的疫苗的免疫原性，2) 已按照 cGMP 进行商业规模生产，3) 已通过FDA 保证人体测试是安全的。因此，本申请提出：1) 确认减毒三价 rVSVN4CT1 载体丝状病毒疫苗将保护猴子免受 EboV 和 MarV 的攻击，2) 在支持未来生产的条件下合规地制备疫苗中三种病毒的种子储备根据 cGMP，3) 使用合规种子储备制备三价疫苗，该疫苗将在非人类灵长类动物中进行 GLP 神经毒理学研究以确认安全性， 4) 在开发研究中使用合规的三价疫苗，以确定具有实际现场使用所需的稳定性特征的冻干制剂，以及 5) 测试冻干三价疫苗以确认其 在暴露前和暴露后施用时，可保护 NHP 免受埃博拉病毒和马病毒的侵害。