Pathogenesis of Chikungunya virus

基孔肯雅病毒的发病机制

• 批准号: 8234196
• 负责人: Mark T Heise
• 金额: $ 20.15万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8234196
• 关键词: Acute; Affect; Africa; Alphavirus; Americas; Antarctica; Antiviral Response; Arthralgia; Arthritis; Asia; B-Lymphocyte Epitopes; Bioterrorism; Categories; Chikungunya virus; Clinical; Culicidae; Development; Disease; Encephalitis Viruses; Epidemic; Equus caballus; Fever; Human; Immune response; In Vitro; Indonesia; Infection; Italy; Kinetics; Licensing; Mammalian Cell; Mediating; Mus; Pathogenesis; Publishing; RNA Viruses; Rage; Research; Ross river virus; T-Lymphocyte; Testing; Therapeutic; USSR; United States National Institutes of Health; Vaccine Design; Vaccines; Viral; Virus; Virus Diseases; biodefense; chikungunya; design; human disease; in vivo; member; mortality; mouse model; therapeutic vaccine; tissue tropism; vaccine candidate; vector mosquito; virus pathogenesis

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.

甲病毒是一组超过25种蚊子传播的单链RNA病毒， 除了南极洲以外的所有大陆都有人类疾病。其中三个是B类精选代理 （委内瑞拉，东部和西部Encephalus病毒），至少有一种（VEE）已被武器化， 美国和苏联的过去。最近一次大规模的VEE流行发生在1995年， 马的大量死亡和超过100，000例人类病例，病例死亡率约为1%。 基孔肯雅热（CHIK）是一种C类病原体，是非洲地方性严重发热性疾病的病因 其特征在于急性和使人衰弱的关节疼痛，其在病毒清除后可持续数月。的 这种病毒已经成为一种流行病，目前有200多万病例席卷印度次大陆， 印度尼西亚，并通过一名受感染的旅行者，现在已经蔓延到意大利。既没有治疗方法， 任何甲病毒的许可人类疫苗。我们建议：1）检查CHIK的发病机制， 最近建立的小鼠模型，该模型再现了其人类临床表现，以及2）产生一种 这种重要的新出现的感染的候选疫苗。此外，我们将扩展已发表的结果， 交叉保护性甲病毒B细胞表位和T细胞介导的抗甲病毒保护作用的最新观察 甲病毒挑战以设计对甲病毒属的多个成员广泛有效的疫苗。 这种实用的方法符合美国国立卫生研究院设计疫苗和治疗有效的任务 对付多名特工