title: Adenoviral Vector Vaccination Induces a Conserved Program of CD8(+) T Cell Memory Differentiation in Mouse and Man.
abstract: Following exposure to vaccines, antigen-specific CD8(+) T cell responses develop as long-term memory pools. Vaccine strategies based on adenoviral vectors, e.g., those developed for HCV, are able to induce and sustain substantial CD8(+) T cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8(+) T cell memory pools induced by an adenovector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include upregulation of homing receptors and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet. In humans, an adenovirus vaccine induced similar CMV-like phenotypes and transcription factor regulation. These data clarify the core features of CD8(+) T cell memory following vaccination with adenovectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK; Department Biomedicine, University of Basel, 4056 Basel, Switzerland. Electronic address: beatrice.bolinger@unibas.ch.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bolinger
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Sims
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Leo
authors.initials: L
authors.lastname: Swadling
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Geraldine
authors.initials: G
authors.lastname: O'Hara
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: de Lara
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Dilair
authors.initials: D
authors.lastname: Baban
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Natasha
authors.initials: N
authors.lastname: Saghal
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Lian Ni
authors.initials: LN
authors.lastname: Lee
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marchi
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Davis
authors.affiliation: Singapore Institute for Clinical Sciences, Agency of Science Technology and Research (A(∗)STAR), Singapore 138632, Singapore.
authors.forename: Evan
authors.initials: E
authors.lastname: Newell
authors.affiliation: ReiThera, Viale Città d'Europa 679, 00144 Roma, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Capone
authors.affiliation: ReiThera, Viale Città d'Europa 679, 00144 Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK; NIHR Biomedical Research Centre, Oxford OX3 9DU, UK.
authors.forename: Ellie
authors.initials: E
authors.lastname: Barnes
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK; NIHR Biomedical Research Centre, Oxford OX3 9DU, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D014157:Transcription Factors