Immune responses to Vibrio cholerae in children

描述（由申请人提供）：本申请为Daniel T. Leung, m.d., m.s.申请五年K08指导临床科学家研究发展奖。该候选人在Beth Israel Deaconess医学中心完成了传染病临床研究，并在马萨诸塞州总医院（MGH）传染病科Edward T. Ryan博士的实验室进行博士后研究培训。拟议的培训计划以Ryan博士为主要导师，将包括以儿童霍乱弧菌感染的免疫反应为重点的教学和实践培训。这项研究建立在MGH与孟加拉国国际腹泻病研究中心（ICDDR，B）之间长期合作的基础上。ICDDR B疫苗科学中心主任Firdausi Qadri博士将为申请人提供共同指导。Stephen B. Calderwood博士，MGH的教授和主任将主持培训咨询小组。霍乱是一种由霍乱弧菌引起的急性脱水腹泻疾病，在50多个国家流行，每年影响200万至300万人，造成10万多人死亡。在流行地区，5岁以下儿童的疾病负担很高。尽管如此，与成人相比，目前可用的霍乱疫苗在幼儿中的效力较低，保护时间也较短。即使在成人中，接种疫苗后的免疫力也是短暂的。相比之下，自然感染后的保护性免疫持续数年，幼儿的保护时间被认为与成人相当。儿童霍乱保护性免疫反应的介质和机制仍然知之甚少。该候选人在过去的24个月里开始着手解决这一缺陷，已前往孟加拉国，并开始描述孟加拉国达卡儿童对霍乱感染和疫苗接种的急性和恢复期免疫反应。在这份申请中，申请人现在提出了一个扩展这些研究的K08职业发展计划，并建立在正在进行的和完全批准的NIAID和SIDA/SAREC支持的项目基础上。该职业发展计划将帮助候选人发展成为一名独立的生物医学研究者，将提高我们对具有全球意义的人类限制性感染期间宿主-病原体事件的理解，并可能导致针对儿童的长效和保护性改进霍乱疫苗，儿童是全球霍乱负担最大的人群。

DESCRIPTION (provided by applicant): This proposal is for a five year K08 Mentored Clinical Scientist Research Development Award for Daniel T. Leung, M.D., M.Sc. This candidate completed a clinical fellowship in Infectious Diseases at Beth Israel Deaconess Medical Center, and has entered post-doctoral research training in the laboratory of Dr. Edward T. Ryan in the Division of Infectious Diseases at Massachusetts General Hospital (MGH). The proposed training plan, with Dr. Ryan as primary mentor, will include both didactic and practical training focused on immune responses of Vibrio cholera infection in children. This research builds upon a longstanding collaboration between MGH and the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). Dr. Firdausi Qadri, Director of Center for Vaccine Sciences at ICDDR,B, will provide co-mentorship to the applicant. Dr. Stephen B. Calderwood, Professor and Chief of ID at MGH will chair the Training Advisory Group. Cholera is an acute dehydrating diarrheal disease caused by Vibrio cholera, endemic in over 50 countries, and affecting 2 to 3 million people each year, causing more than 100,000 deaths. In endemic areas, children under 5 years of age have a high burden of disease. Despite this, currently available cholera vaccines achieve a lower efficacy and a shorter duration of protection in young children compared to that achieved in adults. Even in adults, immunity after vaccination is short-lived. In comparison, protective immunity after natural infection lasts for several years, and duration of protection in young children is thought to be comparable to that of adults. The mediators and mechanism of protective immune response to cholera in children remain poorly understood. The candidate has spent the last 24 months beginning to address this deficiency, has moved to Bangladesh, and has begun to characterize the acute and convalescent immune- responses to cholera infection and vaccination in children in Dhaka, Bangladesh. In this application, the applicant now proposes a K08 career development program that extends these studies, and builds upon ongoing and fully approved NIAID and SIDA/SAREC supported projects. This career development program would assist the candidate in his development into an independent biomedical investigator, would improve our understanding of host- pathogen events during a human restricted infection of global significance, and could lead to a long acting and protective improved cholera vaccine for children, the population that bears the largest global burden of cholera. Public Health Relevance: Cholera is a diarrheal disease affecting millions of people worldwide each year. Compared to natural infection, current oral cholera vaccines provide relatively short-term protection, especially in young children who bear the largest global burden of cholera. We propose a career development program that focuses on advancing our understanding of immune responses to cholera infection and vaccination in children in Bangladesh; such knowledge could lead to an improved cholera vaccine.