title: Early life vaccination: Generation of adult-quality memory CD8+ T cells in infant mice using non-replicating adenoviral vectors.
abstract: Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal priming. Replication deficient adenoviral vectors have been demonstrated to induce potent CD8+ T-cell response in mice, primates and humans. The aim of the present study was therefore to assess whether replication-deficient adenovectors could overcome the risk of overwhelming antigen stimulation during the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate that memory CD8+ T cells induced by adenoviral vectors in infant mice are of good quality and match those elicited in the adult host.
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Loulieta
authors.initials: L
authors.lastname: Nazerai
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Bassi
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ida E M
authors.initials: IE
authors.lastname: Uddback
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Holst
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology / Q000517:prevention & control; D000367:Age Factors; D000818:Animals; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D007109:Immunity; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D015415:Biomarkers; D014612:Vaccines