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

开发 CCHF 免疫测定法以协助 I 期临床试验

• 批准号: 10026656
• 金额: $ 54.28万
• 依托单位: UKHSA
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10026656
• 关键词: Development; immune; assays; CCHF; aid

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.

克里米亚-刚果出血热(CCHF)是一种由壁虱传播的病毒引起的广泛疾病，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、中东和欧洲的扁虱中；最近进入西班牙的病例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，其中一些开始进入第一阶段临床试验。这项计划将发展标准化的免疫化验方法，以评估接种疫苗后产生的符合监管标准的疫苗反应。为了全面衡量免疫力，将测量免疫的两个主要方面：抗体水平和T细胞的反应能力。这项建议将使抗体结合试验标准化，并开发多功能T细胞荧光点试验。在这些检测中使用的高质量抗原的来源包括在这个项目中。这两种分析读数都将基于自动荧光信号，以确保它们是可修改的，以进行验证和符合GxP。一旦分析设计完成，它们将接受正式验证，标准操作程序(SOP)正在制定中，并符合监管批准所需的水平。这些分析和方法将适用于不同的CCHF候选疫苗，允许协调输出并在临床试验之间进行直接比较。重要的是，他们将为多种CCHF候选疫苗的预定和未来进展增加工具包。