Immune responses to Vibrio cholerae in children

描述（由申请人提供）：本提案旨在为丹尼尔T.梁博士，这位候选人在贝斯以色列女执事医疗中心完成了传染病的临床奖学金，并在爱德华T。Ryan在马萨诸塞州总医院（MGH）传染病科工作。拟议的培训计划由Ryan博士担任主要导师，将包括教学和实践培训，重点关注儿童霍乱弧菌感染的免疫反应。这项研究建立在MGH和孟加拉国国际腹泻病研究中心（ICDDR，B）之间的长期合作基础上。ICDDR疫苗科学中心主任Firdausi Qadri博士，B，将为申请人提供共同指导。史蒂芬博士B。Calderwood教授和MGH的ID主管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性腹泻病，在50多个国家流行，每年影响200万至300万人，造成10多万人死亡。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，保护期较短。即使是成年人，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可持续数年，幼儿的保护期被认为与成人相当。儿童对霍乱的保护性免疫反应的介质和机制仍然知之甚少。候选人在过去的24个月里开始解决这一缺陷，已经搬到孟加拉国，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的特点。在本申请中，申请人现在提出了一个K 08职业发展计划，该计划扩展了这些研究，并建立在正在进行和完全批准的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，将提高我们对全球意义的人类有限感染期间宿主病原体事件的理解，并可能为儿童提供长效和保护性的改良霍乱疫苗，儿童是全球霍乱负担最大的人群。 公共卫生相关性：霍乱是一种慢性疾病，每年影响全世界数百万人。与自然感染相比，目前的口服霍乱疫苗提供的保护时间相对较短，特别是对全球霍乱负担最重的幼儿。我们提出了一个职业发展计划，重点是提高我们对孟加拉国儿童霍乱感染和疫苗接种免疫反应的理解;这些知识可能会导致改进霍乱疫苗。

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.