FILOVIRUS ADENO-BASED VACCINES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 埃博拉病毒在人类和非人类灵长类动物(NHP)中引起一种严重的出血性疾病。在人类中，这种疾病对高达90%的感染者是致命的，这取决于爆发中涉及的埃博拉病毒种类。目前，还没有获得许可的疫苗或疗法来预防或治疗埃博拉病毒。通常的预防性公共卫生措施不能应用于埃博拉出血热病例，因为尚未明确确定自然宿主。鉴于生物恐怖主义的风险和非洲埃博拉疫情的反复爆发，迫切需要开发有效的埃博拉病毒疫苗。由于候选埃博拉病毒疫苗不能进行传统的人类疗效试验，因此必须根据美国食品和药物管理局的动物规则获得许可，该规则要求证明对非人类灵长类动物有效。 在研制基于DNA和重组腺病毒载体的埃博拉疫苗方面取得了重大进展。本研究的目的是在非人类灵长类动物中测试腺病毒基埃博拉疫苗和免疫策略，以确定/定义保护的免疫相关因素。将从注射疫苗的动物身上获取血液样本，以评估疫苗诱导的特定免疫反应。疫苗和未接种疫苗的对照组将接触致命剂量的埃博拉病毒，以确定候选疫苗的效力。接种候选疫苗的动物将受到保护，不会接触致命剂量的埃博拉病毒，而未接种疫苗的对照组将死于感染。这些研究的结果将对支持埃博拉疫苗的临床应用提供重要支持。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ebola virus causes a severe hemorrhagic disease in humans and non-human primates (NHP). In humans, the disease is fatal in up to 90% of infected individuals, depending on the Ebola virus species involved in the outbreak. Currently there are neither licensed vaccines nor therapies to prevent or treat Ebola virus. The usual preventive public health measures cannot be applied in the case of Ebola hemorrhagic fever because the natural reservoir has not been positively identified. In light of the risk of bioterrorism and recurrent Ebola outbreaks in Africa, the development of an effective Ebola virus vaccine is urgently needed. Because traditional human efficacy trials cannot be performed for candidate Ebola virus vaccines, licensure will have to be obtained by the Food and Drug Administration's 'Animal Rule' which requires demonstration of efficacy in nonhuman primates. Significant progress has been made towards developing an Ebola vaccine based on DNA and recombinant adenovirus virus vectors. The objective of this study is to test adeno based Ebola vaccines and immunization strategies in nonhuman primates to identify/define immune correlates of protection. Blood samples will be obtained from animals injected with vaccines for assessment of specific vaccine-induced immune responses. Vaccines and unvaccinated controls will be exposed to a lethal dose of Ebola virus to determine the efficacy of candidate vaccines. Animals vaccinated with candidate vaccines will be protected from exposure to a lethal dose of Ebola virus, whilst unvaccinated controls will succumb to infection. The results obtained from these studies will be important in supporting licensure of an Ebola vaccine for clinical application.