Cohen Courtney A, Balinandi Stephen, Kuehne Ana I, Rock Michelle L, Bonagofski Luke G, Ricks Keersten M, Davis Ian, Abelson Dafna, Stonier Spencer W, Odongo Matthew, Bornholdt Zachary A, Zeitlin Larry, Moyer Crystal, Cose Stephen, Dye John M, Lutwama Julius J, Herbert Andrew S
Virology Division, US Army Medical Research Institute of Infectious Disease, Fort Detrick, Maryland, USA.
Department of Arbovirology, Medical Research Council/Uganda Viral Research Institute, Entebbe, Uganda.
J Infect Dis. 2025 Mar 17;231(3):762-772. doi: 10.1093/infdis/jiae395.
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.
评估人类克里米亚-刚果出血热（CCHF）病毒（CCHFV）自然感染幸存者的适应性免疫反应对于开发医学应对措施至关重要。然而，保护的相关因素尚不清楚。作为最常见的蜱传人类出血热病毒，病死率为5%-30%，且分布于全球，迫切需要填补这些知识空白。在此，我们通过对一组乌干达CCHF幸存者进行6年的连续采样，描述了他们的适应性免疫反应。我们证明了感染后持续存在的抗体以及针对各种真实CCHFV毒株的交叉中和作用，以及强大的效应功能。此外，我们首次展示了感染后长达9年对多种CCHFV蛋白持续存在的多功能抗原特异性记忆T细胞反应。这些数据共同为评估CCHFV医学应对措施提供了免疫学基准，以及可用于疫苗免疫原设计和单克隆抗体疗法病毒靶点鉴定的信息。
