Modification of antigen impacts on memory quality after adenovirus vaccination.

The establishment of robust T cell memory is critical for the development of novel vaccines for infections and cancers. Classical memory generatedby CD8+ T cells is characterised by contracted populations homing to lymphoid organs. T cell “memory inflation”, as seen for example after cytomegalovirus infection, is the maintenance of expanded, functional, tissue-associated effector memory cell pools. Such memory pools may also be induced after adenovirus vaccination, and we recently defined common transcriptional and phenotypic features of these populations in mouse and man. However, the rules that govern which epitopes drive memoryinflation compared to classical memory are not fully defined and thus it is not currently possible to direct this process. We used our adenoviral model of memory inflation to first investigate the role of the promoter and then the role of the epitope context in determining memory formation. Specifically, we tested the hypothesis that conventional memory could be converted to “inflationary” memory by simple presentation of the antigen in the form of “minigene” vectors. When epitopes from LacZ and MCMV that normally induce classical memory responses were presented as minigenes, they induced clear memory inflation. These data demonstrate that, regardless of the transgene promoter, the polypeptide context of a CD8+ T cell epitope may determine whether classical or inflating memory responses are induced. The ability to direct this process by the use of minigenes is relevant to the design of vaccines and understanding of immune responses to pathogens