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.

项目摘要（总体） 致病性HENIPAVIRAS（Nipah和Hendra）在Paramyxoviruse中有所区别 他们独特的广泛的往流和令人印象深刻的致命性。这些病毒可以在6个阶面感染动物 哺乳动物，在包括人类在内的11个物种中常常致命疾病。孟加拉国的尼帕特别是 关注，每年发生爆发，案件死亡率接近100％，人与人向人的传播。 目前，尚无批准用于人类使用的疫苗或治疗剂。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经济上重要的牲畜 和澳大利亚。 HENIPAVIRAS是包裹的RNA病毒，它们的生物学使它们可以合成 产生，滥用作为Bioterror或BioWarfare的药物的潜力很高。有重要的 在过去十年中，疫苗开发和尼帕和暴露后疗法的进展 亨德拉。预防性疫苗将对有实验室工人，急救人员或个人高风险有实用性 接触;但是，在生物攻击或自然爆发的情况下，暴露后治疗将是 最实用的方法。 HENIPAVIRUS G和F糖蛋白是中和的主要靶标 抗体和疫苗策略的基石。中心的所有三个研究项目（RP）关注 制定有效的策略，以防止所有致病性HENIPAVIRES。 RP1专注于可溶性Hendra g 糖蛋白疫苗，RP2专注于人类抗融合病毒单克隆抗体，RP3专注于 重组基于雪松病毒的疫苗。该中心的一个独特方面是，它包括两个最大的 研究的对策表明能够提供完整的暴露前后保护 针对尼帕/亨德拉感染的非人类灵长类动物。 RPS中某些进步的水平是 我们中心的主要优势和优势。疫苗和疫苗发展的主要目标 HENIPAVIRUSS中心的疗法是进行关键研究，以促进产品的发展 用于预防和治疗Nipah和Hendra感染。三个RPS之间的合作， 行政核心，人类单克隆抗体核心和生物安全水平（BSL）-4核心已内置 以设计为中心，因为所有组件都可以共同提供广泛有效的对策。质量 系统数据管理将用于高级舞台测试文章的准备和 动物研究的进行。 相关性（总体） 尼帕（Nipah）和亨德拉（Hendra）是对人类和牲畜健康的高度致病性病毒和威胁。他们是 在自然界中可用，可以合成生成，易于产生和传播，并有可能 高死亡率和主要的公共卫生影响。没有批准人类使用的对策。 该中心侧重于最有前途的抗病毒药的高级发展，包括唯一的策略 证明可以对非人类灵长类动物的暴露后保护侵害HENIPAVIRES。

项目成果

Vaccines to Emerging Viruses: Nipah and 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