T-cell immune responses to Vibrio cholerae infection

描述（由申请人提供）：本申请提出了一个为期三年的KOI国际研究科学家职业发展奖的续期，重点是描述t细胞对霍乱弧菌感染的免疫反应。该项目将在博士的合作指导下进行。Stephen B. Calderwood和Edward T. Ryan，马萨诸塞州波士顿马萨诸塞州总医院传染病科，Firdausi Qadri博士，孟加拉国达卡国际腹泻病研究中心实验室科学部。候选人接受过儿科传染病方面的培训，并有书面承诺在国际儿科传染病领域进行独立的临床研究。该提案的研究部分包括三个具体目标：(1)比较霍乱患者和疫苗中CD4+ t细胞对霍乱弧菌抗原的反应特征；(2)评价霍乱患者黏膜CD4+ t细胞反应；(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。导师和支持教师将协助申请人的研究和职业发展的进展。该项目将使候选人发展成为国际儿科传染病的独立生物医学研究人员，根据拟议项目产生的数据将使候选人能够申请独立的NIH资助，用于未来对霍乱和其他肠道感染的免疫反应的研究。

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.