title: DNA vaccines: MHC II-targeted vaccine protein produced by transfected muscle fibres induces a local inflammatory cell infiltrate in mice.
abstract: Vaccination with naked DNA holds great promise but immunogenicity needs to be improved. DNA constructs encoding bivalent proteins that bind antigen-presenting cells (APC) for delivery of antigen have been shown to enhance T and B cell responses and protection in tumour challenge experiments. However, the mechanism for the increased potency remains to be determined. Here we have constructed DNA vaccines that express the fluorescent protein mCherry, a strategy which allowed tracking of vaccine proteins. Transfected muscle fibres in mice were visualized, and their relationship to infiltrating mononuclear cells could be determined. Interestingly, muscle fibers that produced MHC class II-specific dimeric vaccine proteins with mCherry were for weeks surrounded by a localized intense cellular infiltrate composed of CD45+, MHC class II+ and CD11b+ cells. Increasing numbers of eosinophils were observed among the infiltrating cells from day 7 after immunization. The local infiltrate surrounding mCherry+ muscle fibers was dependent on the MHC II-specificity of the vaccine proteins since the control, a non-targeted vaccine protein, failed to induce similar infiltrates. Chemokines measured on day 3 in immunized muscle indicate both a DNA effect and an electroporation effect. No influence of targeting was observed. These results contribute to our understanding for why targeted DNA vaccines have an improved immunogenicity.
authors.affiliation: Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway.
authors.forename: Tom-Ole
authors.initials: TO
authors.lastname: Løvås
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway; Norwegian school of Health Sciences, Kristiania University College, Oslo, Norway.
authors.forename: Jo C
authors.initials: JC
authors.lastname: Bruusgaard
authors.affiliation: Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway.
authors.forename: Inger
authors.initials: I
authors.lastname: Øynebråten
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Gundersen
authors.affiliation: Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway; KG Jebsen Centre for research on Influenza Vaccines, University of Oslo, Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007249:Inflammation / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018485:Muscle Fibers, Skeletal / Q000276:immunology*; D014162:Transfection / Q000379:methods; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D039481:CD11b Antigen; D000949:Histocompatibility Antigens Class II; D019444:Vaccines, DNA; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse