Pathogenesis of Chikungunya virus

甲型病毒是一组超过25种蚊子传播的单链RNA病毒，可引起严重的 除南极洲以外的所有大洲都有人类疾病。其中三个是B类精选代理 (委内瑞拉、东部和西部脑炎病毒)，至少有一种(VEE)已在#年武器化 美国和苏联的过去。最近一次大VEE疫情发生在1995年， 大量马匹死亡和超过10万例人类病例，病例死亡率约为1%。 基孔肯雅(Chik)是一种C类病原体，是非洲地方性严重发热病的病因 以急性和衰弱的关节疼痛为特征，在病毒清除后可持续数月。这个 病毒已经成为一种流行病，目前席卷印度次大陆的病例超过200万例， 印度尼西亚，并通过一名受感染的旅行者，现在已经传播到意大利。既没有治疗方法，也没有 任何甲型病毒的授权人类疫苗。我们建议1)研究CHIK的发病机制 最近建立的概括其人类临床表现的小鼠模型，以及2)产生一种 这一新出现的重要感染的候选疫苗。此外，我们还将把已发表的成果推广到 甲型肝炎病毒B细胞交叉保护性表位及T细胞介导的免疫保护作用的研究进展 甲型病毒挑战，设计一种广泛有效的疫苗，对抗甲型病毒属的多个成员。 这种实用的方法符合美国国立卫生研究院关于设计有效的疫苗和治疗方法的要求。 针对多个特工。

Alphaviruses are a group of over 25 mosquito transmitted single-stranded RNA viruses that cause severe human disease on all continents except Antarctica. Three of these are Category B select agents (Venezuelan, Eastern and Western Encephalitis viruses), and at least one (VEE) has been weaponized in the past by both the U.S. and the Soviet Union. The most recent large VEE epidemic occurred in 1995 with massive equine mortality and over 100,000 human cases with an approximately 1% case mortality rate. Chikungunya (CHIK) is a Category C agent and the cause of endemic severe febrile illness in Africa characterized by acute and debilitating joint pain which can persist for months after viral clearance. The virus has emerged as an epidemic of over 2 million cases currently engulfing the Indian subcontinent and Indonesia, and through an infected traveler, it now has spread to Italy. There are neither therapeutics nor licensed human vaccines for any alphavirus. We propose 1) to examine the pathogenesis of CHIK in a recently established mouse model that recapitulates its human clinical manifestations, and 2) to produce a candidate vaccine for this important emerging infection. Moreover, we will extend published results on cross-protective alphavirus B-cell epitopes and recent observations of T-cell mediated protection against alphavirus challenge to design a vaccine broadly effective against multiple members of the alphavirus genus. This practical approach conforms to the NIH mandate of designing vaccines and therapeutics effective against multiple agents.