Ebola Vaccine Development

埃博拉疫苗开发

• 批准号: 7592427
• 负责人: NANCY J SULLIVAN
• 金额: $ 55.35万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592427
• 关键词: Adenovirus Vector; Clinical Trials; Conduct Clinical Trials; DNA; DNA Vaccines; Disease Outbreaks; Ebola Vaccines; Ebola virus; Frankfurt-Marburg Syndrome Virus; Genes; Human; Immune response; Immunity; Immunization; Infection; Laboratories; Macaca; Modification; Phase; Primates; Testing; Time; Vaccination; Vaccines; Viral Hemorrhagic Fevers; Virus Diseases; immunogenicity; improved; nonhuman primate; plasmid DNA; prevent; vaccine development; vector vaccine

A vaccine against Ebola virus would be highly significant in preventing outbreaks which are both naturally occurring or the result of bioterrorist activity. Modifications to previously developed Ebola vaccines were made during the past year to improve expression and immunogenicity. Ebola and Marburg viruses have been identified as the cause of several highly lethal outbreaks of hemorrhagic fever for which there is no effective treatment or cure. Therefore, vaccine studies are critically important for protection against infection. We developed a highly effective vaccine strategy for Ebola virus infection in non-human primates 1. A combination of primary immunization with plasmid DNA and boosting with adenoviral vectors containing Ebola genes generated protective immunity in cynomolgus macaques. The vaccine yielded 100% protective efficacy against Ebola infection and showed for the first time that protective immune responses could be generated in primates. The DNA vaccine is currently being tested in Phase I human clinical trials conducted by the VRC Clinical Trials Core Laboratory. In addition to our DNA prime/adenoviral vector boost vaccine studies, our laboratory has demonstrated that protective immunity to Ebola can be generated with a single inoculation of adenoviral vector vaccine 2, a result with significant implications for conducting enhanced ring vaccination during an Ebola outbreak.

针对埃博拉病毒的疫苗在防止天然发生或生物恐怖活动的结果方面非常重要。在过去的一年中，对先前开发的埃博拉疫苗进行了修改，以改善表达和免疫原性。 埃博拉病毒和马尔堡病毒已被确定为几次高度致命的出血热暴发的原因，没有有效的治疗或治愈。因此，疫苗研究对于防止感染至关重要。我们开发了一种非人类灵长类动物中埃博拉病毒感染的高效疫苗策略1。一级免疫与质粒DNA的结合，以及与含有埃博拉病毒基因的腺病毒载体相结合，在cynomolgus猕猴中产生了保护性免疫。该疫苗针对埃博拉病毒感染产生了100％的保护疗法，并首次表明可以在灵长类动物中产生保护性免疫反应。目前，在VRC临床试验核心实验室进行的I期人类临床试验中，目前正在对DNA疫苗进行测试。除了我们的DNA Prime/腺病毒载体增强疫苗研究外，我们的实验室还表明，可以通过单次接种腺病毒载体疫苗2来产生对埃博拉病毒的保护性免疫，这一结果对在埃博拉期间在埃博拉期间进行增强的环疫苗接种产生了重大影响。