The role of TcpA in cholera immunity and vaccination

描述(申请人提供)：本申请是为期4年的国际研究科学家发展奖，以研究抗菌免疫和疫苗开发。候选人将在马萨诸塞州波士顿马萨诸塞州总医院的Stephen Calderwood博士和Edward Ryan博士以及孟加拉国达卡ICDDR.B：卫生和人口研究中心(ICDDR.B)的Firdausi Qadri博士的指导下进行。候选人目前正在完成儿科传染病研究奖学金，并计划从事研究发展中国家重要肠道疾病的学术生涯。在拟议的计划中，学员将在ICDDR.B花费至少50%的时间。培训计划将包括侧重于细菌遗传学、免疫学和疫苗开发的课程和研讨会。实践经验将拓宽学员在适应性免疫实验室研究、在人类受试者中进行和分析大型观察性研究以及疫苗开发转化研究所需的实验室技术方面的技能。该提案的重点是提高对霍乱适应性免疫机制的了解。该项目的3个具体目标是：(1)评估TCPA特异性免疫反应是否与预防霍乱有关；(2)评估秘鲁-15减毒霍乱活疫苗是否能诱导与自然霍乱感染类似的免疫反应；以及(3)开发经皮疫苗接种策略，以增强霍乱动物模型中TCPA特异性免疫反应。这项研究计划将使学员能够在初步研究结果的基础上，发展与疫苗开发有关的研究技能，以支持独立的研究事业。相关性：这项研究将增加我们对霍乱免疫力的了解，并可能有助于开发一种霍乱疫苗，该疫苗每年可以挽救发展中国家数千人的生命。

DESCRIPTION (provided by applicant): This application is for a 4-year International Research Scientist Development Award for the study of anti- bacterial immunity and vaccine development. The candidate will be under the mentorship of Dr. Stephen Calderwood and Dr. Edward Ryan at the Massachusetts General Hospital, Boston, Massachusetts, and Dr. Firdausi Qadri, at the ICDDR.B: Centre for Health and Population Research, Dhaka, Bangladesh (ICDDR.B). The candidate is currently completing a fellowship in Pediatric Infectious Diseases and plans to pursue an academic career studying enteric diseases of importance in developing countries. In the proposed program, the trainee will spend at least 50% of his time at the ICDDR.B. The training program will include courses and symposia focused on bacterial genetics, immunology and vaccine development. Hands-on experience will broaden the trainee's skills in the laboratory study of adaptive immunity, in the conduct and analysis of large observational studies in human subjects, and in the laboratory techniques necessary for translational research in vaccine development. The proposal is focused on improving understanding of the mechanisms of adaptive immunity to cholera. 3 specific aims of the project are: (1) to assess whether TcpA-specific immune responses are associated with protection from cholera; (2) to assess whether the Peru-15 live attenuated cholera vaccine induces comparable immune responses to natural cholera infection; and (3) to develop a transcutaneous vaccination strategy to boost TcpA-specific immune responses in an animal model of cholera. This research plan will allow the trainee to build on preliminary findings and to develop research skills related to vaccine development that can be used to support an independent research career. Relevance: This research will increase our understanding of immunity to cholera and may aid in the development of a cholera vaccine that could save thousands of lives each year in developing countries.