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

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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.