Bunyavirus Immunity Consortium: Delineating the immune response against CCHFV and other Nairoviruses to aid effective vaccine design

病毒性出血热的特征是非常高的温度和出血，并与高发病率和死亡率相关。许多病毒可引起甚高频，包括克里米亚-刚果出血热病毒（CCHFV），这是影响人类的最广泛的蜱传病毒性疾病。该病在许多地区流行，如非洲、亚洲、东欧和南欧以及中亚。在疫情暴发期间，与cchfv相关的死亡率估计高达30%。由于需要在高度封闭的实验室中工作，以及相对缺乏容易获得和适当的疾病模型，对影响人类的甚高频气体的研究受到限制。内罗毕绵羊病病毒（NSDV）是一种重要的兽医特异性和自然发生的绵羊和山羊甚高频病毒。小反刍动物感染非sdv与高达90%的高死亡率相关，但对人类的风险较低。NSDV与CCHFV密切相关，对NSDV的调查将为CCHFV工作提供积极的信息，反之亦然，同时增加我们对vhf的了解并有助于为疫苗开发提供信息。暴露于CCHFV和NSDV后的免疫应答保护机制尚不清楚。然而，没有患者再次感染CCHFV的报告，只有当未发病的动物被转移到地方性动物地方病区时，才会发生NSDV疾病暴发；这表明先前的接触会导致保护性免疫。描述CCHFV/ NSDV感染后的免疫反应是本项目的主要目的。通过抗体功能评估、抗原谱分析和b细胞队列评估，将实现VHF后恢复免疫反应的详细研究。还将测量暴露的人和动物中针对CCHF和NSDV的t细胞免疫反应的功能、人群队列和召回反应类型。这将有助于确定产生保护性免疫所需的免疫的广度和范围，并以此方式确定纳入疫苗的蛋白质选择。因此，我们将评估接触神经病毒（例如CCHFV和/或NSDV）后的免疫反应，预计这种免疫分析将确定抗原靶点，成为消除运动中的疫苗成分，这将直接和积极地影响流行国家的经济、健康和福利。这是本研究计划的原则和直接目的。

Viral haemorrhagic fevers (VHF) are characterised by very high temperatures and bleeding, and are associated with high levels of morbidity and mortality. A number of viruses can cause VHF, including Crimean-Congo haemorrhagic fever virus (CCHFV), which is the most widespread, tick-borne viral disease affecting humans. The disease is endemic in many regions, such as Africa, Asia, Eastern and Southern Europe, and Central Asia. CCHFV-associated deaths are estimated to be as high as 30% during outbreak settings. The study of VHFs that affect humans is limited by the need to work in high containment laboratories and by the relative absence of easily-accessible and appropriate models of disease. Nairobi sheep disease virus (NSDV) is an important veterinary-specific and naturally occurring VHF of sheep and goats. NSDV infection of small ruminants is associated with high mortality of up to 90% but is of low risk to humans. NSDV is very closely related to CCHFV, and investigation of NSDV will positively inform CCHFV work and vice versa, whilst simultaneously increasing our knowledge of VHFs and helping inform vaccine development. The immune response that protects post-exposure to CCHFV and NSDV remains unknown. However, there are no reports of patients being re-infected with CCHFV and disease outbreaks of NSDV only occur when naive animals are moved to an enzootic area; suggesting that prior exposure can result in protective immunity. Delineating the immune response following CCHFV/ NSDV infection is the main objective of this project. Detailed studies of the immune response in recovery post VHF will be achieved through the assessment of antibody functionality, antigenic profiling and B-cell cohort evaluation. The functionality, population cohorts and type of recall response for T-cell immune responses against CCHF and NSDV, in exposed humans and animals, will also be measured. This will help define the breadth and repertoire of immunity needed to develop protective immunity and in this manner identify the protein(s) of choice for vaccine inclusion. We will therefore assess the immune responses post exposure to nairoviuses (e.g. CCHFV and/ or NSDV) foreseeing that this immune profiling will identify antigenic targets to become vaccine components in elimination campaigns which will directly and positively impact the economy, health and welfare of endemic countries. This is the principle and direct aim of this research proposal.