Under the aegis of an R21 grant (AI49771: Transgenic B cell immunogens), we developed an antigen-presenting cell (APC)-based vaccine using the influenza A virus as a model system. Studies focused on CD8 T cell memory responses revealed that protection is mediated by CD8 T cells with high CD62L expression. These are referred to as central memory T cells. This finding on the correlate of protection in vivo is now proposed as the basis for a new experiment to understand the requirements to induce protective memory CD8 T cells by vaccination. The hypothesis we wish to test is that successful programming by a genetic APC vaccine of central memory CD8 T cell induction may be subject to a series of considerations of general nature such as dose and interval between priming and encounter with the pathogen, the interaction with the environment such as dendritic cells and IL-15, and the presence of CD62L as a key phenotypic feature of the signature gene. Our objective is to further use the newly developed APC vaccination system as a proof of principle to understand the requirements for the generation of protective central memory CD8 T cells against a category 3 viral pathogen. The importance of our studies is also that the new vaccination approach while built on the cardinal axiom Vaccination--> Immunity--> Protection is intended at inducing protection against disease, hence setting a new target for vaccine-directed control of old or emerging infectious diseases. We believe that our studies will have implications in the development of an alternative approach to effectively vaccinate against influenza A virus using novel APC vaccine approach.
