T-cell immune responses to Vibrio cholerae infection

描述(由申请者提供)：本申请建议将KOI国际研究科学家职业发展奖续期三年，重点是表征对霍乱弧菌感染的T细胞免疫反应。该计划将在马萨诸塞州波士顿马萨诸塞州总医院传染病科的Stephen B.Calderwood博士和Edward T.Ryan博士以及孟加拉国达卡国际腹泻疾病研究中心实验室科学部的Firdausi Qadri博士的合作指导下进行。应聘者接受过儿科传染病方面的培训，并对国际儿科传染病领域的独立临床研究做出了有文件证明的承诺。该建议的研究部分包括三个具体目标：(1)比较霍乱患者和疫苗中的CD4+T细胞对霍乱弧菌抗原的反应特点；(2)评估霍乱患者的粘膜CD4+T细胞反应；以及(3)评估初始CD4+T细胞反应与B细胞对霍乱弧菌记忆的发展和维持之间的关系。导师和支持教师将帮助申请者的研究和职业发展的进展。该计划将允许候选人发展为国际儿科传染病方面的独立生物医学研究人员，根据拟议计划产生的数据将使候选人能够为未来霍乱和其他肠道感染的免疫反应研究申请独立的NIH资金。 与公共卫生相关：据估计，霍乱弧菌每年导致300万至500万例秘书腹泻和100,000多人死亡。虽然有症状的霍乱弧菌感染会产生持久的免疫力，但疫苗未能产生类似的疾病保护作用。更好地了解T细胞对自然霍乱和疫苗接种的反应可能直接导致霍乱疫苗的改进。

DESCRIPTION (provided by applicant): This application proposes a three-year renewal of a KOI International Research Scientist Career Development Award focused on characterizing T-cell immune responses to Vibrio cholerae infection. The program will be conducted under the collaborative mentorship of Drs. Stephen B. Calderwood and Edward T. Ryan, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts and Dr. Firdausi Qadri, Laboratory Sciences Division, International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh. The candidate is trained in Pediatric Infectious Diseases and has a documented commitment to an independent clinical research in the field of international pediatric infectious diseases. The research component ofthe proposal includes three specific aims: (1) To compare the characteristics of CD4+ T-cell responses to V. cholerae antigens in cholera patients and vaccines; (2) To evaluate mucosal CD4+ T-cell responses in cholera patients; and (3) To evaluate the association between initial CD4+ T-cell responses and the development and maintenance of B cell memory to V. cholerae. The mentors and supporting faculty will assist with the progress of the applicant's research and career development. The program will allow the candidate to develop as an independent biomedical researcher in international pediatric infectious diseases, and data generated under the proposed program will enable the candidate to apply for independent NIH funding for future studies of immunologic responses to cholera and other enteric infections. PUBLIC HEALTH RELEVANCE: Vibrio cholerae is estimated to cause 3 to 5 million cases of secretary diarrhea and over 100,000 deaths annually. Although symptomatic infection with V. cholerae results in durable immunity, vaccines have failed to induce comparable protection against disease. An improved understanding of T-cell responses to natural cholera and vaccination may lead directly to improvements in cholera vaccines.