title: Qualitative and quantitative analysis of adenovirus type 5 vector-induced memory CD8 T cells: not as bad as their reputation.
abstract: 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 by directly comparing these cells to CD8 T cells induced through infection with lymphocytic choriomeningitis virus (LCMV). We found that localized immunization with intermediate doses of Ad vector induces a moderate number of functional CD8 T cells which qualitatively match those found in LCMV-infected mice. The 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 led to even higher numbers of memory cells. In this case, the vaccination led to the generation of a population of memory cells characterized by relatively low CD27 expression and high CD127 and killer cell lectin-like receptor subfamily G member 1 (KLRG1) expression. These memory CD8 T cells were capable of proliferating in response to viral challenge and protecting against infection with live virus. Furthermore, viral challenge was followed by sustained expansion of the memory CD8 T-cell population, and the generated memory cells did not appear to have been driven toward exhaustive differentiation. Based on these findings, we suggest that adenovirus-based prime-boost regimens (including Ad serotype 5 [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.
authors.affiliation: University of Copenhagen, Department of International Health, Immunology and Microbiology, Copenhagen, Denmark.
authors.forename: Maria Abildgaard
authors.initials: MA
authors.lastname: Steffensen
authors.forename: Peter Johannes
authors.initials: PJ
authors.lastname: Holst
authors.forename: Sanne Skovvang
authors.initials: SS
authors.lastname: Steengaard
authors.forename: Benjamin Anderschou Holbech
authors.initials: BA
authors.lastname: Jensen
authors.forename: Christina
authors.initials: C
authors.lastname: Bartholdy
authors.forename: Anette
authors.initials: A
authors.lastname: Stryhn
authors.forename: Jan Pravsgaard
authors.initials: JP
authors.lastname: Christensen
authors.forename: Allan Randrup
authors.initials: AR
authors.lastname: Thomsen
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D014764:Viral Proteins; D014765:Viral Vaccines; C115679:glycoprotein peptide, Lymphocytic choriomeningitis virus
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