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

布尼亚病毒免疫联盟：描述针对 CCHFV 和其他内罗病毒的免疫反应，以帮助有效的疫苗设计

• 批准号: BB/R019991/1
• 负责人: Teresa Lambe
• 金额: $ 143.95万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR019991%2F1
• 关键词: Bunyavirus; Immunity; Consortium; Delineating; immune

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.

病毒性出血热 (VHF) 的特点是极高的体温和出血，并且与高发病率和死亡率相关。许多病毒可引起 VHF，包括克里米亚-刚果出血热病毒 (CCHFV)，它是影响人类的最广泛的蜱传病毒性疾病。该病在非洲、亚洲、东欧、南欧以及中亚等许多地区流行。据估计，在疫情爆发期间，与 CCHFV 相关的死亡人数高达 30%。由于需要在高度封闭的实验室中工作以及相对缺乏易于获得和适当的疾病模型，对影响人类的甚高频的研究受到限制。内罗毕绵羊病病毒 (NSDV) 是一种重要的兽医特异性、绵羊和山羊自然产生的 VHF。小反刍动物的 NSDV 感染死亡率高达 90%，但对人类的风险较低。 NSDV 与 CCHFV 密切相关，对 NSDV 的调查将为 CCHFV 工作提供积极信息，反之亦然，同时增加我们对 VHF 的了解并帮助为疫苗开发提供信息。保护接触 CCHFV 和 NSDV 后的免疫反应仍然未知。然而，没有关于患者再次感染 CCHFV 的报道，并且 NSDV 疾病爆发仅在幼崽动物被转移到地方性动物流行地区时发生；表明事先接触可以产生保护性免疫力。该项目的主要目标是描述 CCHFV/NSDV 感染后的免疫反应。将通过抗体功能评估、抗原谱分析和 B 细胞队列评估来对 VHF 后恢复中的免疫反应进行详细研究。还将测量暴露的人类和动物中针对 CCHF 和 NSDV 的 T 细胞免疫反应的功能、人群群体和回忆反应类型。这将有助于确定发展保护性免疫所需的免疫广度和全部，并以这种方式确定疫苗包含的蛋白质选择。因此，我们将评估接触内罗病毒（例如 CCHFV 和/或 NSDV）后的免疫反应，预见到这种免疫分析将识别抗原靶点，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。

项目成果

Generation and Characterisation of Monoclonal Antibodies against Nairobi Sheep Disease Virus Nucleoprotein.

• DOI: 10.3390/v15091876
• 发表时间: 2023-09-05
• 期刊: Viruses
• 作者: Maze EA;Chrun T;Booth G;Limon G;Charleston B;Lambe T
• 通讯作者: Lambe T

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.

• DOI: 10.1016/j.ebiom.2023.104523
• 发表时间: 2023-04
• 期刊: EBIOMEDICINE
• 影响因子: 11.1
• 作者: Saunders, Jack E.;Gilbride, Ciaran;Dowall, Stuart;Morris, Susan;Ulaszewska, Marta;Spencer, Alexandra J.;Rayner, Emma;Graham, Victoria A.;Kennedy, Emma;Thomas, Kelly;Hewson, Roger;Gilbert, Sarah C.;Belij-Rammerstorfer, Sandra;Lambe, Teresa
• 通讯作者: Lambe, Teresa

Risk factors for Crimean-Congo Haemorrhagic Fever (CCHF) virus exposure in farming communities in Uganda.

• DOI: 10.1016/j.jinf.2022.09.007
• 发表时间: 2022-12
• 期刊: JOURNAL OF INFECTION
• 影响因子: 28.2
• 作者: Atim, Stella A.;Ashraf, Shirin;Belij-Rammerstorfer, Sandra;Ademun, Anna R.;Vudriko, Patrick;Nakayiki, Teddy;Niebel, Marc;Shepherd, James;Balinandi, Stephen;Nakanjako, Gladys;Abaasa, Andrew;Johnson, Paul C. D.;Odongo, Steven;Esau, Martin;Bahati, Milton;Kaleebu, Pontiano;Lutwama, Julius J.;Masembe, Charles;Lambe, Teresa;Thomson, Emma C.;Tweyongyere, Robert
• 通讯作者: Tweyongyere, Robert

Development of anti-Crimean-Congo hemorrhagic fever virus Gc and NP-specific ELISA for detection of antibodies in domestic animal sera.

• DOI: 10.3389/fvets.2022.913046
• 发表时间: 2022
• 期刊: Frontiers in veterinary science
• 影响因子: 3.2

The Integration of Human and Veterinary Studies for Better Understanding and Management of Crimean-Congo Haemorrhagic Fever.

• DOI: 10.3389/fimmu.2021.629636
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Gilbride C;Saunders J;Sharpe H;Maze EA;Limon G;Ludi AB;Lambe T;Belij-Rammerstorfer S
• 通讯作者: Belij-Rammerstorfer S