Preclinical development of A CD8 T-Cell Priming Vaccine Against Chikungunya Virus

针对基孔肯雅病毒的 CD8 T 细胞引发疫苗的临床前开发

• 批准号: 10084550
• 金额: $ 229.12万
• 依托单位: EMERGEX VACCINES HOLDING LIMITED
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10084550
• 关键词: Preclinical; development; CD8; Cell; Priming

The project proposes to advance a CD8 T-cell priming Chikungunya virus (CHIKV) vaccine candidate (PepGNP-ChikV) through preclinical development, cGMP manufacture and and MHRA regulatory submission for a Phase-1 clinical trial in the UK. The overall aim of this project is be ready to move into a Phase-1 clinical trial within 3 to 6 months of completion of this project.CHIKV is a mosquito-transmitted alphavirus that causes epidemics of illness characterized by debilitating arthralgia and arthritis that can endure for months to years following infection. In the last decade, CHIKV has become a reemerging mosquito-transmitted virus that has spread into Europe, Asia, the Pacific Region, and the Americas, with epidemics causing severe economic impact. No licensed vaccine exists.Emergex has developed a unique T-cell priming vaccine platform comprised of two technologies: a library of expressed major histocompatibility complex (MHC) Class 1-restricted viral specific peptides, and a self-adjuvating gold nanoparticle (GNP) carrier system. Emergex believes that T-cell priming vaccines offer an effective means to prevent disease and transmission for a range of pathogens including Chikungunya. T-cell priming vaccines have the advantage that since they target human cells at the stage of initial viral infection, they can clear the viral pathogen before it has the opportunity to replicate (Termed "abortive infection"). This would prevent both clinical disease and transmission. The T-cell prime system also has the capacity for long term protection (\>20 years).Using the Emergex platform, two products (A Dengue vaccine and a Betacoronavirus vaccine) have completed Phase-1 trials in Switzerland (NCT04935801 and NCT04935801). The vaccines were shown to be safe and capable of inducing significant vaccine specific T-cell effector and memory responses. Regulatory approval has been given for a phase 1b trial for the betacoranavirus vaccine due to begin imminently. These vaccines will be advanced in Phase-2 trials. A universal influenza vaccine is due to enter a Phase-1 trial in the USA in Q4 this year.This project will advance upon outputs from the previous competition "SBRI - Vaccines for epidemic diseases: Readiness for clinical development and regulatory submission". In this competition Emergex met all milestones and 1) identified the Chikungunya peptide epitope library using immunoproteomics 2) synthesized an experimental vaccine candidate using those epitope sequences 3) Showed in vitro efficacy of the candidate. Based on these outputs, Emergex believe the candidate is now in a state of readiness to enter formal preclinical development and cGMP manufacture.

该项目建议通过临床前开发，cGMP生产和MHRA监管提交来推进CD 8 T细胞引发基孔肯雅病毒（CHIKV）候选疫苗（PepGNP-Chikv），以进行英国的1期临床试验。该项目的总体目标是在完成后3至6个月内准备进入1期临床试验。CHIKV是一种蚊子传播的甲病毒，可引起疾病流行，其特征是关节痛和关节炎，感染后可持续数月至数年。在过去的十年中，CHIKV已经成为一种重新出现的蚊子传播的病毒，已经传播到欧洲，亚洲，太平洋地区和美洲，流行病造成严重的经济影响。Emergex开发了一种独特的T细胞引发疫苗平台，该平台由两种技术组成：表达的主要组织相容性复合体（MHC）1类限制性病毒特异性肽库和自组装金纳米颗粒（GNP）载体系统。Emergex认为，T细胞引发疫苗提供了预防疾病和包括基孔肯雅病毒在内的一系列病原体传播的有效手段。T细胞引发疫苗的优点在于，由于它们在初始病毒感染阶段靶向人类细胞，因此它们可以在病毒病原体有机会复制之前清除病毒病原体（称为“流产感染”）。这将防止临床疾病和传播。使用Emergex平台，两种产品（登革热疫苗和乙型冠状病毒疫苗）已在瑞士完成了1期试验（NCT 04935801和NCT 04935801）。疫苗显示是安全的，并且能够诱导显著的疫苗特异性T细胞效应子和记忆应答。由于开始在即，监管部门已经批准了β-coranavirus疫苗的1b期试验。这些疫苗将在2期试验中取得进展。一种通用流感疫苗将于今年第四季度在美国进入第一阶段试验。该项目将在之前的比赛“SBRI -流行病疫苗：临床开发和监管申报准备就绪”的基础上取得进展。在这次比赛中，Emergex达到了所有里程碑，并且1）使用免疫蛋白质组学鉴定了基孔肯雅肽表位文库2）使用这些表位序列合成了实验疫苗候选物3）显示了候选物的体外功效。根据这些结果，Emergex认为候选人现在已经准备好进入正式的临床前开发和cGMP生产。