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: 8172682
• 负责人: Jean L. Patterson
• 金额: $ 13.22万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172682
• 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; Porcupines; Preparation; Protein Subunits; Recombinants; Research; Research Personnel; Resources; Rodent Model; Source; Technology; Testing; United States National Institutes of Health; Vaccines; Viral Hemorrhagic Fevers; Virus; Zaire Ebola virus; effective therapy; forest; immunogenicity; member; mortality; nonhuman primate; novel vaccines; palliative; pre-clinical; research clinical testing; research study; vaccine candidate

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 丝状病毒科的成员会引起人类和非人类灵长类动物严重的出血热。最重要的成员是埃博拉病毒，自 1976 年首次发现以来，每隔 2-10 年就会周期性地爆发一次。它是 A 类病毒，需要最大限度地控制。在野外，感染是由于人与死亡或垂死的受病毒感染的森林动物接触而引发的，这些动物例如黑猩猩、森林羚羊和豪猪，这些动物经常在受影响地区的雨林地面上发现。扎伊尔埃博拉病毒株通常与死亡率非常高的疫情有关，平均死亡率为 80% 至 90%。除了姑息治疗之外，没有有效的治疗方法。 迄今为止，还没有商业疫苗可以预防丝状病毒感染。先前在小鼠中评估了在昆虫细胞培养系统中表达的埃博拉扎伊尔病毒的三种重组亚基蛋白的免疫原性。实验取得了成功，并导致了疫苗配方的选择，并在活病毒攻击实验（USAMR1ID）中进一步进行了测试。几种制剂可以完全预防由同源病毒株（扎伊尔埃博拉病毒）引起的发病和死亡。非人类灵长类动物在丝状病毒感染后表现出与人类相似的病程，因此被认为是最能预测人类功效的模型。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扎伊尔病毒的免疫原性和功效后，因此必须评估主要候选疫苗的免疫原性和针对非人类灵长类动物活病毒攻击的保护潜力。如果使用新型疫苗免疫后能够证明相关的免疫反应（抗体和成熟淋巴细胞），那么该实验将为该技术提供关键的概念验证。这项研究的成功完成将验证埃博拉疫苗制剂的功效，提前达到临床测试的目标。