Immune responses to Vibrio cholerae in children

儿童对霍乱弧菌的免疫反应

• 批准号: 8517006
• 负责人: Daniel Ted Leung
• 金额: $ 13.72万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8517006
• 关键词: 5 year old; Acute; Address; Adult; Affect; Antibody Formation; Antigens; Area; Bangladesh; Blood typing procedure; Cessation of life; Child; Cholera; Cholera Vaccine; Clinical; Collaborations; Communicable Diseases; Country; Data; Development; Disease; Doctor of Medicine; Evaluation; Event; Fellowship; General Hospitals; Goals; Household; Human; Immune response; Immunity; Immunization; Infection; International; Israel; Knowledge; Laboratories; Lead; Life; Massachusetts; Mediator of activation protein; Medical center; Memory; Memory B-Lymphocyte; Mentored Research Scientist Development Award; Mentors; Mentorship; Micronutrients; National Institute of Allergy and Infectious Disease; Nutritional status; O Antigens; Oral; Patients; Pilot Projects; Plasma; Population; Postdoctoral Fellow; Preschool Child; Research; Research Personnel; Research Training; Science; T cell response; T-Lymphocyte; Training; Ursidae Family; Vaccinated; Vaccination; Vaccines; Vibrio cholerae; blood group; burden of illness; career development; follow-up; improved; international center; killings; pathogen; professor; programs; public health relevance; response; vaccine development; vaccine efficacy

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.

描述（由申请人提供）：本提案旨在为 Daniel T. Leung 医学博士、理学硕士颁发五年期 K08 指导临床科学家研究开发奖。该候选人在贝斯以色列女执事医疗中心完成了传染病临床研究，并已在马萨诸塞州总医院 (MGH) 传染病科 Edward T. Ryan 博士实验室接受博士后研究培训。拟议的培训计划由瑞安博士担任主要导师，将包括侧重于儿童霍乱弧菌感染免疫反应的教学和实践培训。这项研究建立在麻省总医院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,B 疫苗科学中心主任 Firdausi Qadri 博士将为申请人提供共同指导。 MGH 教授兼 ID 主任 Stephen B. Calderwood 博士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2至3百万人，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对幼儿的功效较低，保护持续时间较短。即使在成年人中，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力可持续数年，幼儿的保护持续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 24 个月里开始解决这一缺陷，并移居孟加拉国，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征。在此申请中，申请人现在提出了一个 K08 职业发展计划，该计划扩展了这些研究，并以正在进行且完全批准的 NIAID 和 SIDA/SAREC 支持的项目为基础。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，全球霍乱负担最重的人群。 公共卫生相关性：霍乱是一种腹泻病，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只能提供相对短期的保护，特别是对于承受全球霍乱最大负担的幼儿。我们提出了一项职业发展计划，重点是增进我们对孟加拉国儿童霍乱感染和疫苗接种的免疫反应的了解；这些知识可能会导致改进霍乱疫苗。