Core C: Clinical and Biostatistic Core

登革热和黄热病病毒(YFV)引起一些最重要的蚊媒疾病，包括 世界各地广泛的发病率和死亡率。黄热病病毒引起急性出血热 并发肝炎、肾功能衰竭、凝血功能异常，严重者死亡。目前，有 黄热病在西非和南美洲国家大规模爆发。活的、减毒的黄热病 疫苗(YFV-17D)自20世纪30年代开始使用，在预防黄热病方面非常有效。它 提供超过30年的长期免疫力，最长可达终身。FDA批准了黄热病疫苗 使我们有机会研究潜在的免疫学机制，赋予长期保护 人类的免疫力。登革病毒感染是世界上最流行的蚊媒传染病。 登革热病毒有四种不同但密切相关的血清型(DEN-1、DEN-2、DEN-3和DEN-4)。 从一种血清型感染中恢复并不能对另一种血清型提供保护性免疫。的发病率。 登革热和一种更严重的登革热形式登革热出血热有所增加 在全球范围内，100多个国家40%的人口处于危险之中。理解 自然感染中的保护性免疫反应和长期免疫是疫苗开发的关键。 从这些研究中获得的知识将为安全和有效的登革热所需的免疫反应提供信息 疫苗。在过去和现在的CCHI资助周期中，临床核心一直是Emory的重要组成部分 CCHI计划，并继续支持CCHI科学议程超过10年。核心有三个单元： (1)佐治亚州亚特兰大埃默里大学的希望诊所单元(2)Mahidol Siriraj医院的登革热临床单元 泰国曼谷大学；(3)佐治亚州亚特兰大埃默里大学统计股。在这份提案中，我们计划 继续进行新的先天和细胞免疫研究，以及最先进的单细胞和 集成基因组学以促进我们对免疫记忆、先天免疫、免疫 衰老。希望诊所将继续研究YFV疫苗的临床研究，以提供 项目1、2和3的合适标本。泰国曼谷Siriraj医院的登革热临床单位 将继续对急性感染的儿童和成人进行登革热研究。先天免疫和免疫 斯坦福大学的衰老工作将继续进行。

Dengue and yellow fever viruses (YFV) cause some of the most important mosquito-borne diseases with extensive morbidity and mortality around the world. Yellow fever virus causes an acute hemorrhagic fever complicated by hepatitis, renal failure, coagulation abnormalities, and in severe cases, death. Currently, there are large outbreaks of yellow fever in countries in West Africa and South America. A live, attenuated yellow fever vaccine (YFV-17D) has been in use since the 1930s and is highly efficacious in preventing yellow fever. It provides long-term immunity for over 30 years and up to a life time. The FDA licensed yellow fever vaccine allows us an opportunity to study the underlying immunological mechanisms that confer long term protective immunity in humans. Dengue virus infection is the most prevalent mosquito-borne infectious disease in the world. There are four distinct, but closely related serotypes of dengue virus (DEN-1, DEN-2, DEN-3 and DEN-4). Recovery from infection by one serotype does not provide protective immunity to another. The incidence of dengue fever and a more severe form of dengue known as dengue hemorrhagic fever have increased dramatically worldwide with 40% of world’s population in over 100 countries being at risk. Understanding protective immune responses and long-term immunity in natural infection is key for vaccine development. Knowledge gained from these studies will inform the immune responses needed for a safe and effective dengue vaccine. In the past and current CCHI funding cycles, the Clinical Core has been a vital component of the Emory CCHI program and continues to support the CCHI scientific agenda for over 10 years. The Core has three units: (1) Hope Clinic Unit at Emory University, Atlanta, GA (2) Dengue Clinical Unit at Siriraj Hospital of Mahidol University, in Bangkok, Thailand; (3) Statistical Unit at Emory University, Atlanta, GA. In this proposal, we plan to continue to perform novel innate and cellular immunity studies along with state-of-the art single cell and integrated genomics to advance our fundamental understanding of immune memory, innate immunity, immune senescence. The Hope Clinic Unit will continue studies with the YFV vaccine clinical studies to provide appropriate specimens for Projects 1, 2 and 3. The Dengue Clinical Unit at Siriraj Hospital in Bangkok, Thailand will continue with the dengue studies from acutely infected children and adults. The innate immunity and immune senescence work will continue at Stanford University.