A novel vaccine approach combining mosquito salivary antigens and viral antigens to protect against Zika, chikungunya and other arboviral infections.

寨卡病毒和基孔肯雅热是具有流行潜力的蚊媒病毒，两者都是通过受感染的伊蚊雌性蚊子叮咬传播的。据报道，寨卡病毒和基孔肯雅热疫情已在中南美洲、加勒比海地区、太平洋岛屿、非洲和亚洲爆发。由于全球变暖和森林砍伐，这些病毒有可能通过受感染的旅行者和伊蚊栖息地的扩大在地理上传播。目前还没有疫苗或抗病毒药物来预防或治疗基孔肯雅热和寨卡病毒感染，唯一的保护措施是防止蚊子叮咬。伊蚊也是登革热和黄热病病毒的携带者，而西尼罗河病毒、圣路易斯脑炎和日本脑炎等病毒主要由库蚊传播。受感染的雌性蚊子在探测血液食物以提供产卵所需的营养时，会将病毒沉积到皮肤真皮中。探查触发了不同的炎症通路的激活，以回应蚊子叮咬和病毒感应。蚊子的整个唾液含有帮助控制血液流动的分子，但也含有影响宿主感染过程的分子。驻留在皮肤上的免疫细胞和被叮咬部位招募的细胞很容易受到感染，它们是第一轮病毒复制的宿主，而不是第一道防线。改变对唾液的免疫反应可能会减少病毒在皮肤中的复制，并极大地改变感染过程。ConserV Bioscience设计了一种双组分疫苗：第一组分对所有伊蚊和库蚊都是通用的，旨在阻止蚊子唾液对支持病毒感染的有益影响；第二组分是一种可变组分，针对蚊子携带的病毒的特定区域。在这个项目中，重点是寨卡病毒和基孔肯雅热，但这种方法可以应用于预防其他蚊媒疾病，只需改变第二种病毒特异性成分的靶点。开发一种旨在破坏感染在体内建立的机制的疫苗，结合病原体特异性靶点，是非常有创新性的。该项目将侧重于从现有的潜在候选多肽列表中选择两种疫苗成分的最佳抗原。这两种成分的最佳候选者将分别和合并进行免疫原性和对抗寨卡病毒和基孔肯雅病毒的有效性评估。

Zika and chikungunya are mosquito-borne viruses with epidemic potential, and both are transmitted by the bite of infected _Aedes_ female mosquitoes. Zika and chikungunya outbreaks have been reported in South and Central America, the Caribbean, the Pacific islands, Africa, and Asia. There is a risk that these viruses will spread geographically by infected travellers and by the expansion of _Aedes'_ habitat due to global warming and deforestation. There is currently no vaccine or antiviral to prevent or treat chikungunya and Zika virus infection and the only protection comes from preventing mosquito bites. _Aedes_ mosquitoes are also carriers of dengue and yellow fever viruses whereas viruses such as West Nile, St. Louis encephalitis, and Japanese encephalitis are mainly transmitted by _Culex_ mosquitoes.Infected female mosquitoes deposit virus into the skin dermis as they probe for a blood meal to provide the nutrition required to lay fertile eggs. Probing triggers activation of distinct inflammatory pathways in response to mosquito biting and to virus sensing. Whole mosquito saliva contains molecules that help control blood flow but also contains molecules that influence the course of the infection in the host. Immune cells resident in the skin and cells recruited to the bite site are susceptible to infection, hosting the first round of viral replication rather than being the first line of defence. Modifying the immune response to the saliva could translate in reduced viral replication in the skin and dramatically alter the course of the infection.ConserV Bioscience has designed a two-component vaccine: the first component is common to all _Aedes_ and _Culex_ mosquitoes and aims to stop the beneficial effects that mosquito saliva has on supporting viral infection; the second is a variable component that targets specific regions of viruses carried by mosquitoes. For this project, the focus is on Zika and chikungunya, but this approach could be applied to prevent other mosquito-borne diseases by only requiring a change of target in the second, virus specific component.The development of a vaccine that is aimed at disrupting the mechanism by which infection becomes established in the body, combined with pathogen specific targets, is highly innovative. This project will focus on the selection of the best antigens for the two vaccine components from an existing list of potential peptide candidates. The best candidates for the two components will be evaluated, separately and combined, for immunogenicity and efficacy against both Zika and chikungunya virus.