Advancement of Vaccines and Therapies for Henipaviruses

项目摘要（总体） 致病性亨尼帕病毒（尼帕和亨德拉）在副粘病毒中的区别在于： 它们独特的广泛趋向性和令人印象深刻的杀伤力。这些病毒可以感染6种动物， 哺乳动物，导致包括人类在内的11个物种的致命疾病。孟加拉国的尼帕病毒尤其 疫情每年都有发生，病死率接近100%，并在人与人之间传播。 目前，还没有批准用于人类的疫苗或治疗剂。尼帕和亨德拉是连续的 传染病威胁着整个南亚的公共卫生和重要的经济牲畜 和澳大利亚亨尼帕病毒是有包膜的RNA病毒，其生物学允许它们被合成 生产的生物武器，极有可能被滥用为生物恐怖或生物战剂。取得了重大 过去十年在尼帕疫苗和暴露后疗法的开发方面取得的进展， 亨德拉预防性疫苗对实验室工作人员、第一反应者或高风险个体有用 暴露;但在生物攻击或自然爆发的情况下， 最实用的方法。亨尼帕病毒G和F糖蛋白是中和的主要靶标。 抗体和疫苗策略的基石。中心的三个研究项目（RP）都集中在 开发有效对抗所有致病性亨尼帕病毒的策略。RP 1侧重于可溶性Hendra G 糖蛋白疫苗，RP 2侧重于人抗亨尼帕病毒单克隆抗体，RP 3侧重于 重组雪松病毒疫苗。该中心的一个独特之处在于，它包括两个最- 研究的对策表明，有能力提供完整的暴露前和暴露后保护， 非人灵长类抗尼帕/亨德拉感染。RP中某些进步的水平是 我们中心的主要优势和优势。疫苗发展的主要目标和 亨尼帕病毒治疗中心将进行关键性研究，以促进产品的开发 用于预防和治疗尼帕和亨德拉感染。三个RP之间的合作， 管理核心、人单克隆抗体核心和生物安全等级（BSL）-4核心已内置于 设计中心，因为所有组件协同工作，提供广泛有效的对策。质量 系统数据管理将用于高级阶段试验样品的准备和 进行动物研究。 相关性（总体） 尼帕病毒和亨德拉病毒是高致病性病毒，对人类和牲畜健康都构成威胁。他们是 自然界中存在的，可以合成产生，易于生产和传播，具有潜在的 高死亡率和重大公共卫生影响。没有批准用于人类的对策。 该中心专注于最有前途的抗病毒药物的高级开发，包括唯一的策略 显示为非人灵长类动物提供抗亨尼帕病毒的暴露后保护。

Project Summary (OVERALL) The pathogenic henipaviruses (Nipah and Hendra) are distinguished among the paramyxoviruses by virtue of their uniquely broad tropism and impressive lethality. These viruses can infect animals across 6 orders of mammals, causing an often fatal disease in 11 species including humans. Nipah in Bangladesh is of particular concern, and outbreaks occur annually with near 100% case fatality rates and person-to-person transmission. Currently, there are no vaccines or therapeutics approved for human use. Nipah and Hendra are continuous infectious disease threats both to public health and to economically important livestock throughout South Asia and Australia. The henipaviruses are enveloped RNA viruses and their biology allows them to be synthetically produced, with high potential for misuse as agents of bioterror or biowarfare. There has been significant progress over the last decade in the development of vaccines and postexposure therapies for Nipah and Hendra. Preventive vaccines would have utility for lab workers, first responders or individuals at high risk exposure; but in the case of a biological attack or natural outbreak, a postexposure treatment would be the most practical approach. The henipavirus G and F glycoproteins are the major targets of neutralizing antibodies and the cornerstone of vaccine strategies. All three Research Projects (RP) in the Center focus on developing strategies effective against all pathogenic henipaviruses. RP1 focuses on the soluble Hendra G glycoprotein vaccine, RP2 focuses on human anti-henipavirus monoclonal antibodies, and RP3 focuses on recombinant Cedar virus-based vaccines. A unique aspect of this Center is that it includes both of the most- studied countermeasures that have shown the ability to provide complete pre- and post-exposure protection of nonhuman primates against Nipah/Hendra infection. The level of certain advancements among the RPs is a major strength and advantage of our Center. The primary objective of the Advancement of Vaccines and Therapies for Henipaviruses Center is to perform pivotal studies that will facilitate the development of products used for the prevention and treatment of Nipah and Hendra infections. The cooperation among the three RPs, Administrative Core, human monoclonal antibody Core and Biosafety Level (BSL)-4 Core is built into the Center by design, as all components work together to provide broadly effective countermeasures. Quality system data management will be employed in both the preparation of advanced stage test articles and in the conduct of animal studies. Relevance (OVERALL) Nipah and Hendra, are highly pathogenic viruses and threats to both human and livestock health. They are available in nature, can be synthetically generated and easily produced and disseminated, with the potential for high mortality rates and major public heath impact. There are no countermeasures approved for human use. This Center focuses on the advanced development of the most promising antivirals, including the only strategy shown to offer postexposure protection of nonhuman primates against henipaviruses.