Evaluating the adaptive immune responses to natural infection with Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) in human survivors is critical to the development of medical countermeasures. However, the correlates of protection are unknown. As the most prevalent tick-borne human hemorrhagic fever virus with case fatality rates of 5%–30% and worldwide distribution, there is an urgent need to fill these knowledge gaps. Here, we describe adaptive immune responses in a cohort of Ugandan CCHF survivors via serial sampling over 6 years. We demonstrate persistent antibodies after infection and cross-neutralization against various clades of authentic CCHFV, as well as potent effector function. Moreover, we show for the first time persistent, polyfunctional antigen-specific memory T-cell responses to multiple CCHFV proteins up to 9 years after infection. Together, this data provides immunological benchmarks for evaluating CCHFV medical countermeasures and information that can be leveraged toward vaccine immunogen design and viral target identification for monoclonal antibody therapies.

中文翻译：

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乌干达克里米亚-刚果出血热恢复期幸存者记忆免疫反应的纵向分析


评估人类幸存者对克里米亚-刚果出血热 （CCHF） 病毒 （CCHFV） 自然感染的适应性免疫反应对于制定医疗对策至关重要。但是，保护的相关性尚不清楚。作为最普遍的蜱传人类出血热病毒，病死率为 5%-30%，分布于全球，迫切需要填补这些知识空白。在这里，我们通过连续采样描述了 6 年内乌干达 CCHF 幸存者队列的适应性免疫反应。我们证明了感染和交叉中和后针对真实 CCHFV 的各种分支的持续抗体，以及强大的效应子功能。此外，我们首次显示感染后长达 9 年的持续、多功能抗原特异性记忆 T 细胞对多种 CCHFV 蛋白的反应。总之，这些数据为评估 CCHFV 医疗对策和信息提供了免疫学基准，可用于单克隆抗体疗法的疫苗免疫原设计和病毒靶标鉴定。