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

基孔肯雅病毒（CHIKV）给生活在流行地区的10亿多人带来了沉重的公共卫生负担。CHICKV感染通过受感染蚊子的叮咬传播给人类。它通常不致命，但非常虚弱，有可能母婴传播。CHIKV。非洲、亚洲、美洲、印度洋和太平洋以及欧洲的国家都发生了疫情。CHIKV被认为是一种令人关注的新兴病原体，因为它对温带地区构成威胁，并且存在病毒将被感染的旅行者输入到新地区的风险。该病毒已经能够适应不同的蚊子媒介，遗传分析表明，最近爆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媒介中繁殖。在疫情爆发期间，由于处于感染急性期的人的血液中病毒浓度很高，病毒很容易从人传播到蚊子，然后再传播回人。目前还没有预防CHIKV感染的疫苗或治疗CHIKV感染的药物。这项工作将产生一种完全合成的CD8 T细胞引发疫苗候选物供人类使用。该疫苗将利用由两种技术组成的已建立的平台：特定MHC 1类限制性病毒肽的组合文库和自组装金纳米颗粒载体（GNP）系统。当结合时，这些技术构成了具有简单化学合成、最小冷链要求（在环境温度下稳定性证明>3个月）的全合成疫苗构建体，并且使用微针贴片皮下递送。这些特征使得相对未经训练的个人能够在各种低资源护理环境中快速制造和无针递送。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构建体的人体临床研究。与大多数抗体刺激疫苗相比，Emergex的疫苗策略是“引发”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。然后，病毒特异性效应CD8 T细胞迅速满足疫苗接种后病原体暴露，导致感染细胞被杀死，并阻止产生可能有助于疾病传播的感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，不易发生病毒逃逸突变，并可能提供针对同一家族中一种以上病毒的“交叉反应”免疫。

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.