Proliferation and death of T-cell subsets following vaccination. (360G-Wellcome-079539_Z_06_Z)

The kinetics of T-cell proliferation and death following vaccination in humansare poorly understood. There is an immense effort underway to develop a new generation of vaccines to generate protective T-cell responses against a number of key pathogens responsible for morbidity and mortality on a massive scale. A greater understanding of the processes that lead to effective and durable memory could have a major impact on the design of new vaccines and theimmunization regimes, perhaps allowing development of new adjuvants that enhance survival of memory T-cells following the initial 'burst' response.Labelling dividing cells with deuterium presents a new, safe, radiation-free method of measuring kinetics of antigen-specific T-cells and their subsets. I propose to use this technique to measure T cell responses induced by the tuberculosis vaccine MVA85A in eight healthy BCG-primed volunteers.I will also study apoptosis of vaccine-induced T cells following vaccination with new malaria and tuberculosis vaccines using an apoptosis assay and caspase activation assay. This research will utilise samples from twelve volunteers in upcoming studies in the Oxford clinical trials programme.I also plan to use anti-apoptotic agents in vitro to try modifying this process to increase the size of the resulting memory pool.