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评价细胞培养基和小鼠脑来源的克里米亚-刚果出血热病毒灭活疫苗在短暂免疫抑制(IS)小鼠模型中的效果。

Evaluation of the cell culture based and the mouse brain derived inactivated vaccines against Crimean-Congo hemorrhagic fever virus in transiently immune-suppressed (IS) mouse model.

机构信息

Department of Microbiology, Medical Faculty, Erciyes University, Kayseri, Turkey.

Vaccine Research, Development and Application Center, Erciyes University, Kayseri, Turkey.

出版信息

PLoS Negl Trop Dis. 2020 Nov 23;14(11):e0008834. doi: 10.1371/journal.pntd.0008834. eCollection 2020 Nov.

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the Nairoviridae family within the Bunyavirales order of viruses. Crimean-Congo hemorrhagic fever (CCHF) is the most widespread among tick-borne human viral diseases. It is endemic in many areas of Africa, Asia, the Middle East, in the Balkans, Russia and countries of the former Soviet Union. The confirmed CCHF cases were seen in Spain in 2016 to signify expansion of the virus into new geographical areas. CCHFV causes a viral human disease characterized by sudden onset of fever, headache, abdominal pain, nausea, hypotension, hemorrhage, and hepatic dysfunction with fatality rates up to 30%. Currently, there are no spesific treatments or licensed vaccines available for CCHFV. The absence of a susceptible animal model for CCHFV infection was severely hindered work on the development of vaccines. However, several animal models of CCHFV infection have been recently developed and used to assess vaccine efficacy. In this study, we have used the transiently immune-suppressed (IS) mouse model that MAb-5A3 was used to block IFN-I signaling in immune intact, wild-type mice at the time of CCHFV infection to evaluate the immune response and efficacy of the cell culture based and the mouse brain derived inactivated vaccines against CCHFV. Both vaccine preparations have provided complete protection but the cell culture based vaccine more effectively induced to CCFHV spesific antibodies and T cell responses. This is the first comparison of the cell culture based and the mouse brain derived vaccines for assessing the protective efficacy and the immunogenicity in the IS mouse CCHFV model.

摘要

克里米亚-刚果出血热病毒(CCHFV)是一种属于布尼亚病毒科的蜱传病毒,属于病毒的 Bunyavirales 目。克里米亚-刚果出血热(CCHF)是最广泛传播的蜱传人类病毒性疾病之一。它在非洲、亚洲、中东、巴尔干地区、俄罗斯和前苏联国家的许多地区流行。2016 年在西班牙确认了克里米亚-刚果出血热病例,这表明该病毒已扩展到新的地理区域。CCHFV 引起一种病毒性人类疾病,其特征为突然发热、头痛、腹痛、恶心、低血压、出血和肝功能障碍,死亡率高达 30%。目前,尚无针对 CCHFV 的特定治疗方法或许可疫苗。由于缺乏适合 CCHFV 感染的动物模型,严重阻碍了疫苗的开发工作。然而,最近已经开发并使用了几种 CCHFV 感染的动物模型来评估疫苗的疗效。在这项研究中,我们使用了短暂免疫抑制(IS)小鼠模型,即在 CCHFV 感染时使用单抗 5A3 阻断免疫完整的野生型小鼠中的 IFN-I 信号,以评估细胞培养和小鼠脑源灭活疫苗对 CCHFV 的免疫反应和疗效。两种疫苗均提供了完全保护,但细胞培养疫苗更有效地诱导了针对 CCFHV 的特异性抗体和 T 细胞反应。这是首次在 IS 小鼠 CCHFV 模型中比较细胞培养和小鼠脑源疫苗以评估保护效力和免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3eb/7721194/92a6dc4bac35/pntd.0008834.g001.jpg

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