TY - JOUR

T1 - Qualitative and quantitative analysis of Ad5 vector induced memory CD8 T cells

T2 - not as bad as their reputation

AU - Steffensen, Maria Abildgaard

AU - Holst, Peter Johannes

AU - Steengaard, Sanne Skovvang

AU - Jensen, Benjamin Anderschou Holbech

AU - Bartholdy, Christina

AU - Stryhn, Anette

AU - Christensen, Jan Pravsgaard

AU - Thomsen, Allan Randrup

PY - 2013/3/27

Y1 - 2013/3/27

N2 - 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.

AB - 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.

U2 - 10.1128/JVI.00465-13

DO - 10.1128/JVI.00465-13

M3 - Journal article

C2 - 23536658

VL - 87

SP - 6283

EP - 6295

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 11

ER -