title: Targeting of non-dominant antigens as a vaccine strategy to broaden T-cell responses during chronic viral infection.
abstract: In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilitates potent virus-induced T-cell responses against immunodominant epitopes during subsequent challenge with highly invasive virus. In contrast, when an immunodominant epitope was included in the vaccine, the T-cell response associated with viral challenge remained focussed on that epitope. Early after challenge with live virus, the CD8+ T cells specific for vaccine-encoded epitopes, displayed a phenotype typically associated with prolonged/persistent antigenic stimulation marked by high levels of KLRG-1, as compared to T cells reacting to epitopes not included in the vaccine. Notably, this association was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted by vaccination. In addition, our findings suggest that prior adenoviral vaccination is not likely to negatively impact the long-term and protective immune response induced and maintained by a vaccine-attenuated chronic viral infection.
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark; Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Peter J
authors: PJ
authors: Holst
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
authors: Benjamin A H
authors: BA
authors: Jensen
authors: Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Emeline
authors: E
authors: Ragonnaud
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
authors: Allan R
authors: AR
authors: Thomsen
authors: Department of International Health, Immunology and Microbiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
authors: Jan P
authors: JP
authors: Christensen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D014764:Viral Proteins; D014765:Viral Vaccines