Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, United States of America.
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS Negl Trop Dis. 2020 Aug 13;14(8):e0008637. doi: 10.1371/journal.pntd.0008637. eCollection 2020 Aug.
Development of vaccines and therapies against Crimean-Congo hemorrhagic fever virus (CCHFV) have been hindered by the lack of immunocompetent animal models. Recently, a lethal nonhuman primate model based on the CCHFV Hoti strain was reported. CCHFV Hoti caused severe disease in cynomolgus monkeys with 75% lethality when given by the intravenous (i.v.) route.
METHODOLOGY/PRINCIPAL FINDINGS: In a series of experiments, eleven cynomologus monkeys were exposed i.v. to CCHFV Hoti and four macaques were exposed i.v. to CCHFV Afghanistan. Despite transient viremia and changes in clinical pathology such as leukopenia and thrombocytopenia developing in all 15 animals, all macaques survived to the study endpoint without developing severe disease.
CONCLUSIONS/SIGNIFICANCE: We were unable to attribute differences in the results of our study versus the previous report to differences in the CCHFV Hoti stock, challenge dose, origin, or age of the macaques. The observed differences are most likely the result of the outbred nature of macaques and low animal numbers often used by necessity and for ethical considerations in BSL-4 studies. Nonetheless, while we were unable to achieve severe disease or lethality, the CCHFV Hoti and Afghanistan macaque models are useful for screening medical countermeasures using biomarkers including viremia and clinical pathology to assess efficacy.
由于缺乏免疫功能健全的动物模型，克里米亚-刚果出血热病毒（CCHFV）的疫苗和疗法的开发受到了阻碍。最近，报道了一种基于 CCHFV Hoti 株的致死性非人类灵长类动物模型。当通过静脉内（i.v.）途径给予 CCHFV Hoti 时，Hoti 会导致食蟹猴发生严重疾病，致死率为 75%。
方法/主要发现：在一系列实验中，11 只食蟹猴通过静脉内途径暴露于 CCHFV Hoti，4 只猕猴通过静脉内途径暴露于 CCHFV 阿富汗株。尽管所有 15 只动物都出现了短暂的病毒血症和临床病理学变化，如白细胞减少和血小板减少，但所有猕猴均存活至研究终点，未出现严重疾病。
结论/意义：我们无法将我们的研究结果与之前的报告之间的差异归因于 CCHFV Hoti 株、挑战剂量、来源或猕猴的年龄的差异。观察到的差异很可能是由于猕猴的杂交性质以及 BSL-4 研究中出于必要性和伦理考虑通常使用的动物数量较少所致。尽管我们未能实现严重疾病或致死性，但 CCHFV Hoti 和阿富汗猕猴模型可用于通过病毒血症和临床病理学等生物标志物筛选医疗对策，以评估疗效。
