Recombinant Subunit Vaccine for Tick-Borne Encephalitis

描述（由申请人提供）：蜱传脑炎（TBE）是一种由蜱传脑炎组黄病毒引起的神经系统疾病，可导致高达60%出现临床症状的个体死亡。幸存者通常表现出严重的长期神经后遗症。除了在流行地区通过媒介蜱虫自然感染外，高传染性病毒还可通过食物或以雾化形式传播。因此，开发一种TBE病毒疫苗是美国国立卫生研究院高度优先的生物防御项目。目前可获得的基于灭活全病毒的商业疫苗没有在美国注册，显示出相当大的疫苗副作用，并且不能完全保护人们免受更具毒性的远东亚型。该项目的具体目标是研究重组亚基蛋白与临床相关佐剂联合使用在TBE小鼠模型中对两种主要亚型TBE病毒的保护作用。测试的配方将是抗原和选定的现代佐剂的单一或组合。阳性结果将导致在第二阶段以及在第二个动物模型中进行多组分候选疫苗试验。一种基于重组亚基蛋白的安全有效的疫苗将有助于保护美国公民免受TBEV感染，而无需大规模培养高传染性病毒

DESCRIPTION (provided by applicant): Tick-borne encephalitis (TBE) is a neurological disease caused by Flaviviruses of the tick-borne encephalitis group and causes death in up to 60% of the individuals developing clinical symptoms. Survivors often show severe long-term neurological sequelae. In addition to natural infection via vector ticks in endemic areas, the highly infective viruses can be transmitted via food or in aerosolized form. Therefore, development of a TBE virus vaccine is a NIH high-priority biodefense project. Currently available commercial vaccines based on inactivated whole virus are not registered in the U.S., show considerable vaccination side-effects and do not provide complete protection against the more virulent Far-Eastern subtype. The specific goal of this project is to investigate the efficacy of recombinant subunit proteins used with clinically relevant adjuvants to achieve protection in the mouse model of TBE against both major subtypes of TBE viruses. Tested formulations will be single or combinations of antigens and selected modern adjuvants. Positive results will lead to multicomponent candidate vaccine testing in phase II also in a second animal model. A safe and efficacious vaccine based on recombinant subunit proteins would provide useful in protecting U.S. citizens from TBEV infection without the need of large-scale culture of highly infectious virus