Preclinical Development of a Crimean-Congo Hemorrhagic Fever Virus Vaccine

克里米亚-刚果出血热病毒疫苗的临床前开发

• 批准号: 10655324
• 负责人: Thomas William Geisbert
• 金额: $ 73.99万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655324
• 关键词: Advanced Development; Africa; Animal Model; Animals; Applications Grants; Arboviruses; Attenuated; Biological Assay; Biological Products; Biological Sciences; Biology; Bioterrorism; Category A pathogen; Clinical Treatment; Cluster randomized trial; Containment; Country; Crimean Hemorrhagic Fever; Crimean-Congo Hemorrhagic Fever Virus; Cyclic GMP; Dengue Virus; Disease; Disease Outbreaks; Dose; Ebola; Ebola Hemorrhagic Fever; Ebola virus; Effectiveness; GTP-Binding Proteins; Generations; Genomic Segment; Geography; Glycoproteins; Goals; Guinea; HIV Vaccine Trials Network; HIV vaccine; Head; Health Personnel; Human; Immunization; Knockout Mice; Laboratories; Lassa virus; Lead; Licensing; Life; Macaca fascicularis; Marburgvirus; Medical; Modeling; Mus; National Institute of Allergy and Infectious Disease; National Security; Nature; Pathogenicity; Pharmaceutical Preparations; Phase; Preventive vaccine; Public Health; Recombinant Vaccines; Recombinants; Reporter; Research; Research Personnel; Surface; Treatment Protocols; United States Food and Drug Administration; Vaccination; Vaccines; Vesicular stomatitis Indiana virus; Viral Hemorrhagic Fevers; Virulence; Virus; Virus Diseases; World Health Organization; bioweapon; cross immunity; design; emerging pathogen; high risk; immunogenic; immunogenicity; lead candidate; manufacture; medical countermeasure; neurovirulence; next generation; nonhuman primate; open label; pre-clinical; preclinical development; prevent; protective efficacy; prototype; research and development; tick-borne; tick-borne virus; vaccine candidate; vaccine delivery; vaccine development; vaccine immunogenicity; vaccine trial; vector; vector vaccine

PROJECT SUMMARY/ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne emerging pathogen that causes severe and often fatal hemorrhagic fever in humans across a broad geographic range that includes more than 30 countries. The NIAID lists CCHFV as a Category A priority pathogen, a biological agent that poses the highest risk to national security and public health. CCHF is of particular importance to public health as there are no licensed vaccines or treatments available for use in humans, and because of the concern that the virus could be used as an agent of biological terrorism. The goal of this project is to advance the development of a recombinant vaccine based on next generation vesicular stomatitis virus (rVSV) vectors expressing the CCHFV glycoprotein as a potential medical countermeasure that can provide protection across all six genetically distinct clades of CCHFV. This application proposes to develop and pre-clinically validate a rVSV vectored CCHF vaccine. Next generation Vesiculovax™ CCHF vaccines will be compared head-to-head with a prototype rVSV vaccine that has been shown to completely protect animals against lethal CCHFV infection. Vaccines will be compared for immunogenicity, lack of neurovirulence, and the ability to protect STAT-1 knockout mice against all six M segment clades of CCHFV. A lead candidate vaccine will then be down selected. Supporting studies using a newly developed lethal nonhuman primate model of CCHFV will be employed to confirm protective efficacy of the lead vaccine candidate, assess the ability to the vaccine to provide rapid protection, and finally to begin to determine correlates of protection. This proposal will draw together expertise in vaccine development, CCHFV biology, and animal modeling needed to develop a vaccine that meets both the outbreak and bioweapon scenarios that require rapid protection against all CCHFV clades with a single administration.

项目摘要/摘要 克里米亚 - 康哥出血热病毒（CCHFV）是一种tick传播的新兴病原体，会导致严重和 在包括30多个国家的广泛地理范围内，人类经常致命的出血热。 NIAID将CCHFV列为一种优先病原体，这是一种生物学剂，对 国家安全和公共卫生。 CCHF对公共卫生特别重要，因为没有许可 疫苗或治疗方法可用于人类，并且由于担心该病毒可以用作 生物恐怖主义的代理人。该项目的目的是推进重组疫苗的开发 基于下一代囊泡口腔炎病毒（RVSV），表达CCHFV糖蛋白作为一种 潜在的医学对策可以为CCHFV的所有六个截然不同的进化枝提供保护。 该应用程序提出开发和临时验证RVSV载体的CCHF疫苗。下一代 Vesiculovax™CCHF疫苗将与原型RVSV疫苗进行比较 显示可完全保护动物免受致命CCHFV感染的影响。将比较疫苗 免疫原性，缺乏神经病毒以及保护STAT-1敲除小鼠对所有六个M的能力 CCHFV的片段进化枝。然后，将选择铅候选疫苗。支持研究 新开发的致命的非人类非人类CCHFV私人模型将用于确认保护性效率 候选铅疫苗，评估疫苗提供快速保护的能力，最后开始 确定保护的相关性。该建议将汇集疫苗开发方面的专业知识，CCHFV 生物学和动物建模需要开发符合暴发和生物武器的疫苗 需要快速保护所有CCHFV进化枝的场景。