LASSA FEVER VACCINE EFFICACY IN MARMOSETS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 拉萨病毒(LASV)是一种东半球的阿拉伯病毒，也是拉萨出血热(LHF)的病原体，每年在西非造成多达30万人感染。大约30%的感染导致各种疾病，从轻微的流感样疾病到致命的LHF，每年导致数千人死亡。巨大的疾病负担、严重的并发症、致命性以及LASV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。携带非致病性Mopeia LASV和RdRp突变主要结构蛋白的ML29拉沙热候选疫苗在豚鼠和恒河猴中减毒。我们已经证明，ML29疫苗可以保护豚鼠免受同源和异种LASV毒株的致死性感染。在这里，我们报告了疫苗在非人类灵长类动物中的效果。用1000pfu的ML29免疫6只猕猴，第30天用致死剂量的LASV-Josiah攻击。第二组(n=4)，即未接种疫苗的对照组，感染相同剂量的LASV。观察动物的临床症状，并采集血液进行血液学和血液化学检查。突出的组织病理学表现包括肝脏坏死和靶组织细胞的免疫表型改变，证实了致死性人类LHF的免疫抑制表型。

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.