Steffensen, Maria Abildgaard5; Holst, Peter Johannes6; Steengaard, Sanne Skovvang4; Jensen, Benjamin Anderschou Holbech7; Bartholdy, Christina5; Buus, Anette Stryhn6; Christensen, Jan Pravsgaard6; Thomsen, Allan Randrup6
1 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet2 Genome Research and Molecular Bio Medicine, Department of Biology, Faculty of Science, Københavns Universitet3 Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet4 Department of International Health, Immunology and Microbiology, University of Copenhagen5 Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet6 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet7 Genome Research and Molecular Bio Medicine, Department of Biology, Faculty of Science, Københavns Universitet
not as bad as their reputation
It has been reported that adenovirus (Ad) primed CD8 T cells may display a distinct and partially exhausted phenotype. Given the practical implications of this claim, we decided to analyze in detail the quality of Ad-primed CD8 T cells directly comparing these cells to CD8 T cells induced through infection with lymphocytic choriomeningitis virus. We found that localized immunization with intermediate doses of Ad vector induce a moderate number of functional CD8 T cells, which qualitatively match those found in LCMV-infected mice. Numbers of these cells may be efficiently increased by additional adenoviral boosting and, importantly, the generated secondary memory cells cannot be qualitatively differentiated from those induced by primary infection with replicating virus. Quantitatively, DNA priming prior to Ad-vaccination will lead to even higher numbers of memory cells. In this case, the vaccination leads to the generation of a population of memory cells characterized by relatively low CD27 expression and high CD127 and KLRG1 expression. These memory CD8 T cells are capable of proliferating in response to viral challenge, and protect against infection with live virus. Furthermore, viral challenge is followed by sustained expansion of the memory CD8 T-cell population, and the generated memory cells do not appear to have been driven towards exhaustive differentiation. Based on these findings, we suggest that adenovirus based prime-boost regimens (including Ad5 and Ad5-like vectors) represent an effective means to induce a substantially expanded, long-lived population of high-quality transgene-specific memory CD8 T cells.
Journal of Virology, 2013, Vol 87, Issue 11, p. 6283-6295