PRE-CLINICAL TESTING OF FILOVIRUS VACCINES IN NONHUMAN PRIMATES

非人灵长类动物丝状病毒疫苗的临床前测试

• 批准号: 7716179
• 负责人: RICARDO CARRION
• 金额: $ 7.73万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716179
• 关键词: Affect; Animals; Antelopes; Antibodies; Area; Categories; Cavia; Cell Culture System; Computer Retrieval of Information on Scientific Projects Database; Containment; Democratic Republic of the Congo; Disease; Disease Outbreaks; Drug Formulations; Ebola Vaccines; Ebola virus; Family member; Filoviridae; Filovirus; Floor; Funding; Goals; Grant; Human; Immune response; Immunization; Infection; Insecta; Institution; Life; Mature Lymphocyte; Measures; Modeling; Morbidity - disease rate; Mus; Pan Genus; Pan troglodytes; Porcupines; Preparation; Protein Subunits; Rate; Recombinants; Research; Research Personnel; Resources; Rodent Model; Source; Technology; Testing; United States National Institutes of Health; Vaccines; Viral Hemorrhagic Fevers; Virus; Zaire Ebola virus; concept; forest; immunogenicity; member; mortality; nonhuman primate; novel vaccines; pre-clinical; research clinical testing; research study

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. Members of the family Filoviridae cause severe hemorrhagic fevers in humans and nonhuman primates. The most prominent member, Ebola virus, causes outbreaks periodically at 2-10 year intervals since initial identification in 1976. It is a Category A agent and requires manipulation at maximum containment. In the wild, infections initiate from contact of people with dead or dying virus-infected forest animals such as chimpanzees, forest antelope and porcupines that have been regularly found on the rainforest floor in affected areas. The Zaire strain of Ebola is most often associated with outbreaks with very high mortality rates, on average between 80 to 90%. Apart from palliative measures, there is no effective treatment for the disease. To date, no commercial vaccine is available to protect against infection with filoviruses. The immunogenicity of three recombinant subunit proteins of Ebola Zaire virus expressed in an insect cell culture system was previously evaluated in mice. The experiments were successful and led to the selection of vaccine formulations that have further been tested in a live virus challenge experiment (at USAMRlID). Several formulations elicited complete protection against morbidity and mortality caused by the homologous virus strain (Ebola Zaire). Nonhuman ,primates show a similar course of disease upon filovirus infection as humans and are therefore considered to be the model most predictive of human efficacy. After successful demonstration of immunogenicity and efficacy against Ebola Zaire virus in two rodent models (mice and guinea pigs), the leading vaccine candidates therefore have to be evaluated for immunogenicity and protective potential against live virus challenge in non-human primates. If relevant immune responses (antibody and mature lymphocytes) can be demonstrated after immunization with the novel vaccines, this experiment will provide the pivotal proof-of-concept for the technology. Successful completion of this study will validate the efficacy of the Ebola vaccine preparations in advance to the goal of clinical testing.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Fileviridae家族成员在人类和非人类灵长类动物中引起严重的出血性发作。自1976年初次识别以来，最著名的成员埃博拉病毒会定期以2 - 10年的间隔引起爆发。它是一种代理类别，需要在最大遏制下进行操作。在野外，感染是由死亡或垂死的感染病毒感染的森林动物（例如黑猩猩，森林羚羊和豪猪）的人接触，这些动物经常在受影响地区的雨林楼层发现。埃博拉的扎伊尔菌株通常与死亡率很高的暴发有关，平均在80％至90％之间。除了姑息治疗措施外，该疾病还没有有效的治疗方法。 迄今为止，尚无商业疫苗来防止丝状病毒感染。先前在小鼠中评估了在昆虫细胞培养系统中表达的三种重组亚基蛋白的免疫原性。这些实验是成功的，并导致了在实时病毒挑战实验中进一步测试的疫苗制剂（在USAMRLID上）。几种配方引起了完全保护由同源病毒菌株（埃博拉Zaire）引起的发病率和死亡率的完全保护。非人类的灵长类动物在丝状病毒感染时表现出类似的疾病病程，因此被认为是最可预测人类功效的模型。因此，在两种啮齿动物模型（小鼠和豚鼠）中成功证明了针对埃博拉Zaire病毒的免疫原性和功效后，必须评估领先的候选疫苗的候选物，以评估免疫原性和保护潜在的潜在，以防止非人类灵长类动物的生命病毒挑战。如果在用新型疫苗免疫后可以证明相关的免疫反应（抗体和成熟的淋巴细胞），则该实验将为该技术提供关键的概念概念。这项研究的成功完成将验证埃博拉疫苗制剂的疗效，以实现临床测试的目标。