Advancement of Vaccines and Therapies for Henipaviruses

亨尼帕病毒疫苗和治疗的进展

• 批准号: 10581491
• 负责人: CHRISTOPHER C BRODER
• 金额: $ 563.18万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-20 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581491
• 关键词: Adjuvant; Advanced Development; Animal Diseases; Animal Model; Animals; Antiviral Agents; Asia; Attenuated; Attenuated Vaccines; Australia; Bangladesh; Biological Warfare; Biology; Case Fatality Rates; Classification; Collaborations; Combined Modality Therapy; Communicable Diseases; Data; Data Management Resources; Disease; Disease Outbreaks; Dose; Drug Kinetics; Effectiveness; Ensure; Evaluation; Formulation; Freeze Drying; Future; Glycoproteins; Goals; Health; Hendra Virus; Henipavirus; Human; Immune; Individual; Infection; Infectious Diseases Research; Liquid substance; Livestock; Mammals; Monoclonal Antibodies; Morbidity - disease rate; Mutation; Nature; Nipah Virus; Paramyxovirus; Pathogenicity; Persons; Preparation; Prevention; Preventive vaccine; Procedures; Process; Production; Public Health; RNA Viruses; Recombinants; Research Institute; Research Project Grants; Respiratory Disease; Science; Subunit Vaccines; System; Testing; Therapeutic; Translational Research; Transportation; Tropism; United States Dept. of Health and Human Services; Vaccines; Viral; Viral Vaccines; Virus; Virus Diseases; Work; aluminum sulfate; clinical development; design; evaluation/testing; first responder; glycoprotein G; high risk; human disease; human monoclonal antibodies; immunogenicity; improved; mortality; nanoparticle; nervous system disorder; neutralizing antibody; nonhuman primate; novel; outbreak concern; particle; pathogenic virus; prevent; product development; programs; protective efficacy; transmission process; vaccine development; vaccine platform; vaccine strategy

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.

项目总结(总体) 致病性黑尼帕病毒(Nipah和Hendra)区别于副粘病毒的主要原因是 它们独特的广阔取向和令人印象深刻的杀伤力。这些病毒可以感染6个目的动物 在包括人类在内的11个物种中引起一种通常是致命的疾病。孟加拉的尼帕是特别的 令人关切的是，每年都会发生疫情，病死率接近100%，并在人与人之间传播。 目前，还没有被批准用于人类的疫苗或治疗药物。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 还有澳大利亚。埃尼帕病毒是有包膜的rna病毒，它们的生物学特性允许它们被人工合成。 生产的，极有可能被误用为生物恐怖或生物武器的制剂。已经有了重大的 在过去十年中，Nipah和Nipah的疫苗和暴露后治疗的开发进展 亨德拉。预防性疫苗将对实验室工作人员、急救人员或高危个人有用 暴露；但在发生生物攻击或自然暴发的情况下，暴露后治疗将是 最实用的方法。埃尼帕病毒G和F糖蛋白是中和的主要目标 抗体和疫苗战略的基石。该中心的所有三个研究项目(RP)都侧重于 制定有效对抗所有病原性埃尼帕病毒的策略。RP1专注于可溶性Hendra G 糖蛋白疫苗，RP2侧重于人抗埃尼帕病毒单抗，RP3侧重于 重组雪松病毒疫苗。该中心的一个独特之处在于，它包括最多的- 研究的对策表明，能够在暴露前和暴露后提供完整的保护 非人灵长类动物抗Nipah/Hendra感染。RPS中的某些进步的水平是 我们中心的主要优势和优势。疫苗和疫苗发展的主要目标是 亨尼帕病毒治疗中心将进行关键研究，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RPS之间的合作， 管理核心、人类单抗核心和生物安全级别(BSL)-4核心被内置于 通过设计居中，因为所有组件协同工作以提供广泛有效的对策。质量 系统数据管理将用于高级阶段测试文件的准备和 进行动物研究。 相关性(总体) Nipah和Hendra是高致病性病毒，对人和牲畜的健康都构成威胁。他们是 在自然界中可用，可合成并容易生产和传播，具有潜在的 高死亡率和重大公共卫生影响。目前还没有被批准用于人类使用的对策。 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 显示可为非人类灵长类动物提供暴露后保护，使其免受埃尼帕病毒的侵袭。

项目成果

Vaccines to Emerging Viruses: Nipah and Hendra.

新兴病毒的疫苗：Nipah和Hendra。

• DOI: 10.1146/annurev-virology-021920-113833
• 发表时间: 2020-09-29
• 期刊: Annual review of virology
• 影响因子: 11.3
• 作者: Amaya M;Broder CC
• 通讯作者: Broder CC

Serological evidence of a pararubulavirus and a betacoronavirus in the geographically isolated Christmas Island flying-fox (Pteropus natalis).

• DOI: 10.1111/tbed.14579
• 发表时间: 2022-09
• 期刊: TRANSBOUNDARY AND EMERGING DISEASES
• 影响因子: 4.3
• 作者: Pulscher, Laura A.;Peel, Alison J.;Rose, Karrie;Welbergen, Justin A.;Baker, Michelle L.;Boyd, Victoria;Low-Choy, Samantha;Edson, Dan;Todd, Christopher;Dorrestein, Annabel;Hall, Jane;Todd, Shawn;Broder, Christopher C.;Yan, Lianying;Xu, Kai;Peck, Grantley R.;Phalen, David N.
• 通讯作者: Phalen, David N.

Structure and design of Langya virus glycoprotein antigens.

琅琊病毒糖蛋白抗原的结构与设计。

• DOI: 10.1101/2023.08.20.554025
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Wang,Zhaoqian;McCallum,Matthew;Yan,Lianying;Sharkey,William;Park,Young-Jun;Dang,HaV;Amaya,Moushimi;Person,Ashley;Broder,ChristopherC;Veesler,David
• 通讯作者: Veesler,David