The Role of TCPA in Cholera Immunity and Vaccination

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.<P> 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.<P> 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. <P> 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. <P> 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.