Development of a CD8 T-Cell Priming Vaccine Against Chikungunya Virus

开发针对基孔肯雅病毒的 CD8 T 细胞引发疫苗

• 批准号: 10025629
• 金额: $ 62.5万
• 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: 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=10025629
• 关键词: Development; CD8; Cell; Priming; Vaccine

Chikungunya virus (CHIKV) imparts a high public health burden with more than a billion people living in endemic areas. CHICKV infection is spread to people by the bite of an infected mosquito. It is not often fatal but is very debilitating, with the potential for mother to child transmission. CHIKV. Outbreaks have occurred in countries in Africa, Asia, the Americas, the Indian and Pacific Oceans, and Europe. CHIKV is considered an emerging pathogen of concern because it poses a threat to temperate regions and there is a risk that the virus will be imported to new areas by infected travelers. The virus has been able to adapt to different mosquito vectors, and genetic analysis suggests that the increased severity of recent outbreaks may be due to viral mutation that enables the virus to multiply more easily in a mosquito vector. During outbreaks, due to the high concentration of virus in the blood of those in the acute phase of infection, the virus can readily circulate from humans to mosquitoes and back to humans. There is no vaccine to prevent or medicine to treat CHIKV infection.The proposed effort will generate a fully synthetic CD8 T-Cell priming vaccine candidate for human use. The vaccine will utilize an established platform comprised of two technologies: a combinatorial library of specific MHC Class 1-restricted viral peptides, and a self-adjuvating gold nanoparticle carrier (GNP) system. When combined, these technologies constitute a fully synthetic vaccine construct with a simple chemical synthesis, minimal cold chain requirements (stability demonstrated for \>3 months at ambient temperature) and is delivered subcutaneously using micro-needle patches. These characteristics enable rapid manufacturing and needle-free delivery by relatively untrained individuals in a diversity of low resourced care settings. Emergex has completed preclinical toxicology and initiated human clinical studies with several vaccine constructs utilizing the same technology.In contrast to the majority of antibody-stimulating vaccines, Emergex's vaccine strategy is to 'prime' CD8+ T 'killer' cells. The vaccine is designed to promote the natural cellular immune response to infection. A post-vaccination pathogen exposure is then rapidly met by virus-specific effector CD8 T-Cells, resulting in the killing of infected cells and preventing the ability to produce infectious virus particles that may contribute to disease transmission. This vaccine strategy is anticipated to provide decades-long immune memory, be less prone to viral escape mutation, and may offer 'cross reactive' immunity against more than one virus in the same family.

基孔肯雅病毒（CHIKV）给生活在流行地区的10多亿人带来了沉重的公共卫生负担。鸡病毒感染是通过受感染蚊子的叮咬传播给人类的。它通常不致命，但非常虚弱，有可能母婴传播。CHIKV。疫情发生在非洲、亚洲、美洲、印度洋和太平洋以及欧洲的国家。CHIKV被认为是一种令人关注的新出现病原体，因为它对温带地区构成威胁，并且存在由受感染的旅行者将病毒输入新地区的风险。该病毒已经能够适应不同的蚊子载体，遗传分析表明，最近暴发的严重程度增加可能是由于病毒突变，使病毒更容易在蚊子载体中繁殖。在疫情暴发期间，由于处于感染急性期的人血液中的病毒浓度很高，病毒很容易从人传播给蚊子，然后再传播给人。目前还没有预防或治疗CHIKV感染的疫苗或药物。这项工作将产生一种完全合成的CD8 t细胞启动疫苗，用于人类。该疫苗将利用由两种技术组成的既定平台：特定MHC 1类限制性病毒肽的组合文库和自佐剂金纳米颗粒载体（GNP）系统。当这些技术结合在一起时，构成了一种完全合成的疫苗结构，具有简单的化学合成，最低的冷链要求（在环境温度下证明稳定性为100个月），并使用微针贴片皮下递送。这些特点使得在各种资源匮乏的医疗环境中，相对未经培训的个人能够快速生产和无针交付。Emergex已经完成了临床前毒理学研究，并利用相同的技术启动了几种疫苗结构的人体临床研究。与大多数抗体刺激疫苗不同，Emergex的疫苗策略是“启动”CD8+ T“杀伤”细胞。该疫苗旨在促进对感染的自然细胞免疫反应。疫苗接种后的病原体暴露很快就会被病毒特异性效应CD8 t细胞处理，导致被感染的细胞被杀死，并阻止产生可能导致疾病传播的传染性病毒颗粒的能力。这种疫苗策略预计将提供长达数十年的免疫记忆，不容易发生病毒逃逸突变，并可能提供针对同一家族中多种病毒的“交叉反应性”免疫。