Development of immune assays for CCHF to aid Phase I clinical trials

克里米亚-刚果出血热（CCHF）是一种由蜱传病毒引起的广泛传播的疾病，可导致多次病毒性出血热暴发，病死率为10- 40%。该病毒存在于非洲，亚洲，中东和欧洲的蜱虫中;最近引入西班牙与人类临床病例有关。几种不同的CCHF候选疫苗正在通过临床前试验取得进展，其中一些开始进入I期临床试验。这项计划会发展标准化的免疫测试，以评估疫苗接种后产生的反应，而这些反应是否符合规管标准。为全面量度免疫力，我们会量度免疫力的两个主要方面：抗体水平及T细胞的反应能力。该方案将改进抗体结合试验，并开发多功能T细胞FluoroSpot试验。本项目包括用于这些检测的高质量抗原的来源。两种检测试剂盒的读数均基于自动荧光信号，确保其可用于验证和GxP合规性。一旦设计出检测试剂盒，将通过正在制定的标准操作规程（SOP）进行正式验证，并符合监管批准所需的水平。这些试验和方法将适用于不同的CCHF候选疫苗，允许输出的协调和临床试验之间的直接比较。重要的是，它们将为多种CCHF候选疫苗的计划和未来发展添加工具包。

Crimean-Congo Haemorrhagic Fever (CCHF) is a widespread disease caused by a tick-borne virus which causes several viral haemorrhagic fever outbreaks, with a case fatality rate of 10-40%. The virus is present in ticks across Africa, Asia, the Middle East and Europe; with recent introduction into Spain associated with human clinical cases. Several different vaccine candidates for CCHF are being progressed through preclinical trials with some starting to enter Phase I clinical trials. This project will develop standardised immune assays for assessing vaccine responses generated after immunisation which meet regulatory standards.To give an overall measurement of immunity, the two main arms of immunity will be measured: the levels of antibodies and the ability of T-cells to respond. This proposal will standardise an antibody-binding assay and develop a multifunction T-cell FluoroSpot assay. The sourcing of high-quality antigens for use in these assays are included within this project. Both assay readouts will be based on automated fluorescence signals ensuring that they are amendable for validation and GxP compliance.Once assays have been designed, they will undergo formal validation with standard operating procedures (SOPs) being developed and compliant to the level required for regulatory approval. These assays and methodology will be applicable across different CCHF vaccine candidates, allowing the harmonisation of outputs and direct comparison between clinical trials. Importantly, they will add to the toolkit for scheduled and future advancement of the multiple CCHF vaccine candidates.