Preclinical development of a vaccine for Nipah virus

尼帕病毒疫苗的临床前开发

• 批准号: 10576335
• 负责人: Thomas William Geisbert
• 金额: $ 115.9万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-11 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576335
• 关键词: Advanced Development; Aman; Animals; Antibodies; Awareness; Bangladesh; Biological Assay; Biological Markers; Biological Response Modifier Therapy; Biotechnology; COVID-19 pandemic; Case Fatality Rates; Categories; Category C pathogen; Cells; Centers for Disease Control and Prevention (U.S.); Classification; Cluster randomized trial; Collaborations; Containment; Data; Development; Disease; Disease Outbreaks; Dose; Ebola; Ebola Hemorrhagic Fever; Ebola virus; Effectiveness; Encephalitis; Epidemic; European Union; Fatality rate; Fever; Funding; GTP-Binding Proteins; Genetic Complementation Test; Glycoproteins; Government Agencies; Guinea; Health Personnel; Henipavirus; Human; Human Resources; Immunity; India; Infection; Injections; Laboratories; Lassa virus; Licensing; Malaysia; Mammals; Marburgvirus; Methods; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Nature; Nipah Virus; Oryctolagus cuniculus; Pathogenicity; Pathologic; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Positioning Attribute; Preventive vaccine; Process; Publications; Qualifying; Recombinant Vaccines; Recombinants; Recommendation; Recording of previous events; Regulatory Affairs; Reporting; Research; Research Personnel; Respiratory Disease; Safety; Singapore; Stomatitis; Toxicology; United States Food and Drug Administration; United States National Institutes of Health; Vaccination; Vaccines; Vesicular stomatitis Indiana virus; Viral Vaccines; Virus; Virus Diseases; Work; World Health Organization; Zoonoses; animal rule; biomarker identification; cell bank; experience; improved; manufacturing process; medical countermeasure; mortality; nervous system disorder; neurotoxicity; nonhuman primate; open label; outbreak control; pandemic disease; pandemic potential; pathogen; phase I trial; pre-Investigational New Drug meeting; preclinical development; prevent; priority pathogen; product development; programs; research and development; respiratory pathogen; transmission process; vaccine development; vaccine evaluation; vaccine platform; vaccine safety; vector vaccine

PROJECT SUMMARY/ABSTRACT Nipah virus (NiV) causes febrile encephalitis and severe respiratory disease in humans with fatality rates as high as 100% in some outbreaks (average ~ 75% for outbreaks over the last decade). There are currently no licensed vaccines or therapies for combating NiV disease. NiV is classified as a Biosafety Level (BSL)-4 pathogen because of the high mortality rates associated with infection, the lack of effective medical countermeasures, and the ease of transmission. In addition to causing morbidity and mortality as a naturally acquired infection, NiV is also categorized as a Category C priority pathogen by several US Government agencies because of the concern for deliberate misuse. Importantly, NiV was recently included on the World Health Organization’s (WHO) 2018 List of Priority Pathogens. As a result of the unprecedented global pandemic of COVID-19 there is heightened concern and awareness regarding respiratory pathogens. Consequently, in March of 2020 the US CDC recommended that NiV be added to the list of Tier 1 Select Agents. Studies to develop effective countermeasures have been hampered by the highly pathogenic nature of NiV and its restriction to BSL-4 containment. An effective prophylactic vaccine would find application with medical personnel and close contacts during outbreaks and with laboratory workers engaged in research. A vaccine based on recombinant G protein deleted (ΔG) vesicular stomatitis virus (rVSVΔG) pseudotyped with the glycoproteins (GP) of a number of high consequence viruses have been shown to completely protect nonhuman primates (NHP) against Ebola, Marburg, and Lassa viruses. In addition, the effectiveness of a rVSV-vectored vaccine in preventing Ebola virus disease was demonstrated in a ring vaccination, open-label, cluster-randomised trial in Guinea during the 2013-16 Ebola epidemic. This vaccine was recently licensed as ERVEBO by the European Union and US FDA. Recently, we developed replication-restricted rVSV NiV vaccine vectors expressing the NiV glycoproteins. Importantly, we showed that these vaccines can completely protect NHPs against high dose lethal NiV Bangladesh strain challenge when used as single injection vaccines. This new data is critically important in the context of containing outbreaks as the most effective vaccine in containing a respiratory pathogen and preventing a pandemic is a vaccine that works rapidly with a single administration. Development of a replication restricted platform that provides improved safety without compromising efficacy is a highly significant advancement and can be applied to other viruses with pandemic potential. The main objective of this proposal is to develop a rVSV-based vaccine against NiV (rVSV-NiVBG) that can provide both rapid protection and long term immunity against the most prevalent and pathogenic Bangladesh strain of NiV and to identify biomarkers that can be used to predict protection. In regard to product development, work will also be done to generate research cell bank (RCB) and viral vaccine bank (RVB), a manufacturing process, and conduct of GLP-safety toxicology.

项目摘要/摘要 NIPAH病毒（NIV）导致死亡率高的人类高热脑炎和严重的呼吸道疾病 在某些暴发中100％（过去十年中暴发的平均爆发〜75％）。目前没有许可 阴道或疗法打击NIV疾病。 NIV被归类为生物安全水平（BSL）-4病原体 由于与感染有关的死亡率很高，缺乏有效的医疗对策以及 易于传输。除了引起发病率和死亡率作为自然收到的感染外，NIV是 由于担心 故意滥用。重要的是，NIV最近被包括在世界卫生组织（WHO）2018 优先病原体列表。由于covid-19的前所未有的全球大流行，因此加剧了 对呼吸道病原体的关注和意识。因此，在2020年3月美国CDC 建议将NIV添加到第1层选择代理的列表中。开发有效对策的研究 NIV的高致病性及其限制BSL-4遏制受到阻碍。有效 预防性疫苗会在暴发期间与医务人员和密切联系 实验室工人从事研究。基于重组G蛋白的疫苗已删除（ΔG）囊泡 口腔炎病毒（RVSVΔG）用糖蛋白（GP）拟型多种高后期病毒 已证明可以完全保护非人类隐私（NHP）免受埃博拉病毒，马堡和Lassa病毒的侵害。 此外，证明了RVSV载体疫苗在预防埃博拉病毒疾病中的有效性 在2013 - 16年埃博拉病毒流行期间，在几内亚的环形疫苗接种，开放标签，聚集的试验中。这 疫苗最近被欧盟和美国FDA授予Ervebo。最近，我们开发了 表达NIV糖蛋白的复制限制RVSV NIV疫苗向量。重要的是，我们表明 这些疫苗可以完全保护NHP免受高剂量致命的NIV孟加拉国应变挑战 用作单一注射疫苗。在包含爆发的背景下，这些新数据至关重要 含有呼吸道病原体和预防大流行的最有效的疫苗是一种疫苗 与单个管理迅速合作。开发一个可提供改进的复制限制平台 没有受损效率的安全性是一个极大的进步，可以应用于其他病毒 具有大流行潜力。该提案的主要目的是开发针对NIV的基于RVSV的疫苗 （RVSV-NIVBG）可以提供快速保护和长期免疫，以防止最普遍的疫苗 NIV的致病孟加拉国菌株，并鉴定可用于预测保护的生物标志物。关于 对于产品开发，还将完成研究细胞库（RCB）和病毒疫苗库的工作 （RVB），一种制造过程和GLP - 安全毒理学的行为。