Pathogenesis of Chikungunya virus

基孔肯雅病毒的发病机制

• 批准号: 8375894
• 负责人: Mark T Heise
• 金额: $ 21.32万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8375894
• 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.

α病毒是一组超过25个蚊子传播的单链RNA病毒，引起严重 除南极以外的所有大陆的人类疾病。其中三个是B类选择代理 （委内瑞拉，东部和西部脑炎病毒），至少有一个（VEE）被武器化 美国和苏联的过去。最新的大VEE流行病发生在1995年 大量的马死亡率和超过100,000例人类病例，病例死亡率约为1％。 Chikungunya（Chik）是C类代理商，是非洲特有严重高热病的原因 以急性和衰弱的关节疼痛为特征，病毒清除后几个月可以持续存在。这 病毒已成为目前吞没印度次大陆和 印度尼西亚，通过受感染的旅行者，它已经传播到意大利。既没有治疗剂也没有 任何α病毒的许可人类疫苗。我们建议1）检查A中Chik的发病机理 最近建立的小鼠模型概括了其人类的临床表现，2）产生 这种重要的新兴感染的候选疫苗。此外，我们将扩展发布的结果 交叉保护α病毒B细胞表位和最近对T细胞介导的保护的观察结果 α病毒挑战以设计针对α病毒属的多个成员的疫苗。 这种实用的方法符合NIH设计疫苗和治疗剂有效的任务 针对多个代理。