A bivalent vaccine against the two major arthritogenic alphaviruses: Chikungunya and Mayaro

针对两种主要致关节炎甲病毒：基孔肯雅病毒和马亚罗病毒的二价疫苗

• 批准号: 10086193
• 金额: $ 113.82万
• 依托单位: UNIVERSITY OF OXFORD
• 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=10086193
• 关键词: bivalent; vaccine; against; two; major

In this project, our goal is to develop a bivalent (dual) vaccine against two major viruses associated with arthritis: Chikungunya and Mayaro viruses. These alphaviruses are re-emerging mosquito-borne viruses that cause severe arthritis that can persist for years after the onset for up to half of the patients. Chikungunya virus (CHIKV), the most prominent arthritogenic alphavirus, has caused massive outbreaks impacting millions globally. Mayaro virus (MAYV) is an arthritogenic alphavirus similar to CHIKV. Despite only currently reported in Latin America, it is considered as another potential epidemic virus. These arboviruses are primarily transmitted by _Aedes_ mosquitoes, and their global dissemination highlights the potential threat of CHIKV and MAYV, placing millions at risk worldwide. Despite underreporting, recent studies indicate an overall increase in CHIKV infections in the Americas, Western Africa, and Southeast Asia. Presently, there are no specific drugs or available vaccines against these viruses.The urgent need for a safe and effective vaccine to shield at-risk populations from outbreaks and guard against future epidemics is pressing, especially for those in resource-limited and crowded settings. The global impact of CHIKV remains underestimated, even though studies suggest that CHIKV could pose a more significant burden than any other vector-borne virus due to the debilitating chronic arthritis causing prolonged disease burden and substantial economic losses. Our experience with viral vector vaccines for CHIKV and MAYV suggests that this system, similar to the one used for the Oxford-AstraZeneca COVID-19 vaccine, can elicit a potent immune response. The mRNA technology, proven effective and safe during the COVID-19 pandemic, could expedite the production of a vaccine in response to an outbreak. Therefore, we propose to develop a Chikungunya and Mayaro bivalent vaccine utilizing both viral-vector and mRNA technologies to speed up the creation of a product that can protect against these viruses in this project. Additionally, we will set up virus neutralisation assays to evaluate our bivalent vaccines' neutralisation capacity, supporting clinical development and bolstering the UK's ability to respond swiftly to emerging infections.

在这个项目中，我们的目标是开发一种针对与关节炎相关的两种主要病毒的二价（双重）疫苗：基孔肯雅病毒和马亚罗病毒。这些甲病毒是重新出现的蚊媒病毒，可导致严重的关节炎，多达一半的患者在发病后可持续数年。基孔肯雅病毒（CHIKV）是最突出的致关节炎甲病毒，已引起大规模爆发，影响全球数百万人。马亚罗病毒（Mayaro virus，MAYV）是一种与CHIKV相似的致关节炎甲病毒。尽管目前仅在拉丁美洲报告，但它被认为是另一种潜在的流行病毒。这些虫媒病毒主要由伊蚊传播，它们的全球传播突出了CHIKV和MAYV的潜在威胁，使全球数百万人处于危险之中。尽管报告不足，但最近的研究表明，美洲，西非和东南亚的CHIKV感染总体增加。目前，没有针对这些病毒的特效药或疫苗，迫切需要一种安全有效的疫苗，以保护高危人群免受疫情的影响，并预防未来的流行病，特别是对那些资源有限和拥挤的环境。CHIKV的全球影响仍然被低估，尽管研究表明CHIKV可能比任何其他媒介传播的病毒造成更大的负担，因为慢性关节炎会导致长期的疾病负担和巨大的经济损失。我们在CHIKV和MAYV病毒载体疫苗方面的经验表明，这种系统与牛津-阿斯利康COVID-19疫苗所用的系统类似，可以引发有效的免疫应答。mRNA技术在COVID-19大流行期间被证明是有效且安全的，可以加快疫苗的生产以应对疫情的爆发。因此，我们建议利用病毒载体和mRNA技术开发基孔肯雅和马亚罗双价疫苗，以加快创建可以在该项目中保护这些病毒的产品。此外，我们将建立病毒中和试验，以评估我们的二价疫苗的中和能力，支持临床开发，并增强英国对新出现的感染作出迅速反应的能力。