LASSA FEVER VACCINE EFFICACY IN MARMOSETS

拉沙热疫苗对狨猴的功效

• 批准号: 7957899
• 负责人: Jean L. Patterson
• 金额: $ 29.47万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-06 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957899
• 关键词: Africa; Animals; Attenuated; Biological Warfare; Blood Chemical Analysis; Callithrix; Callithrix jacchus jacchus; Cavia; Cells; Cessation of life; Clinical; Computer Retrieval of Information on Scientific Projects Database; Control Groups; Disease; Dose; Funding; Grant; Hematological Disease; Hematology; Histopathology; Human; Immunosuppressive Agents; Infection; Influenza; Institution; Lassa Fever; Lassa virus; Macaca mulatta; Mutate; Old World Arenaviruses; Phenotype; Primates; Reporting; Research; Research Personnel; Resources; Source; Structural Protein; Tissues; United States National Institutes of Health; Vaccinated; Vaccines; Viral Hemorrhagic Fevers; burden of illness; hepatic necrosis; nonhuman primate; vaccine candidate; vaccine development; vaccine efficacy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lassa virus (LASV), an Old World Arenavirus and the etiological agent of Lassa hemorrhagic fever (LHF), causes up to 300,000 annual infections in West Africa. Approximately 30% of infections result in disease varying from mild influenza-like illness to lethal LHF causing several thousand deaths per year. The large disease burden, severe complications, lethality and the possibility that LASV can be used as a biological warfare agent make a strong case for effective vaccine development. A ML29 Lassa fever vaccine candidate carrying mutated major structural proteins of LASV and RdRp of non-pathogenic Mopeia is attenuated in guinea pigs and rhesus macaques. We have shown that ML29 vaccine protects guinea pigs from lethal infection with homologous and heterologous LASV strains. Here we report the efficacy of the vaccine in nonhuman primates. Six marmosets (Callithrix jacchus) were vaccinated with 1000 PFU of ML29 and challenged on day 30 with lethal dose of LASV-Josiah. A second group of marmosets (n=4), the unvaccinated control group, was infected with the same dose of LASV. Animals were observed for clinical signs of disease and blood was collected for hematology and blood chemistry. Prominent histopathology findings included hepatic necrosis and immunophenotypic alterations of cells in target tissues confirming immunosuppressive phenotype of fatal human LHF.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 拉沙病毒 (LASV) 是一种旧世界沙粒病毒，也是拉沙出血热 (LHF) 的病原体，在西非每年导致多达 30 万例感染。 大约 30% 的感染会导致各种疾病，从轻微的流感样疾病到致命的 LHF，每年导致数千人死亡。 LASV 巨大的疾病负担、严重的并发症、致命性以及可用作生物战剂的可能性，为有效开发疫苗提供了强有力的理由。 一种 ML29 拉沙热候选疫苗携带 LASV 和非致病性 Mopeia 的 RdRp 突变主要结构蛋白，在豚鼠和恒河猴中被减毒。 我们已经证明 ML29 疫苗可以保护豚鼠免受同源和异源 LASV 毒株的致命感染。 在这里，我们报告了该疫苗在非人类灵长类动物中的功效。 六只狨猴 (Callithrix jacchus) 接种了 1000 PFU 的 ML29，并在第 30 天用致死剂量的 LASV-Josiah 进行攻击。第二组狨猴（n=4），即未接种疫苗的对照组，感染相同剂量的 LASV。观察动物的疾病临床体征并收集血液进行血液学和血液化学分析。 重要的组织病理学发现包括肝坏死和靶组织中细胞的免疫表型改变，证实了致命性人类 LHF 的免疫抑制表型。