Immunological memory is characterized by the ability of the immune system to respond specifically and more rapidly upon a subsequent encounter with a pathogen or antigen. This specific and rapid recall response defines the basis for vaccination whose goal it is to induce long-term protective immunity. The memory T cell population is very heterogeneous, and whose number, tissue location, and fitness can greatly impacttheir ability to protect against re-infection. It is clear that multiple factors are important for the initial T cell priming but what are less clear are the effects different vaccine vectors and routes of immunization have on the development of T cell memory. To address this we have compared CD8 T cell memory generated after DNA vaccination or influenza infection with LCMV viral infection. We previously have found that DNA vaccine vectors delivered via intramuscular injection produce lesser quality memory CD8 T cells compared to LCMV infection. We have extended our study address if different DNA delivery mechanisms, in this case electroporation combined with intramuscular injection, can have a greater impact on the quality of the resulting CD8 T cell memory. Compared to intramuscular injection alone electroporation resulted in a 2-fold higher number of antigen-specific memory CD8 T cells. However our preliminary results suggest thatanalogous to our previous studies the DNA memory CD8 T cells were suboptimal compared to those generated after LCMV infection. Influenza viruses remain one of the most medically important pathogens, which cause significant morbidity and mortality annually. Using DNA microarrays we compared the gene expression profiles of memory CD8 T cells generated after intranasal influenza infection with those generated after a systemic LCMV infection. Interestingly we found very little differences in the geneexpression profiles. The influenza memory cells showed a decrease in IFN-? and IL-2 gene expression, and an increase in a number of genes involved in the negative regulation of cell cycle. These findings may partially explain why influenza memory cells are suboptimal compared to LCMV memory cells. Our data demonstrates that the programming of memory CD8 T cells by both DNA and influenza may not be optimaland importantly for vaccine development clearly demonstrates that different vaccine vectors can generate different quality memory cells.
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