title: Myristoylation increases the CD8+T-cell response to a GFP prototype antigen delivered by modified vaccinia virus Ankara.
abstract: Activation of CD8(+)T-cells is an essential part of immune responses elicited by recombinant modified vaccinia virus Ankara (MVA). Strategies to enhance T-cell responses to antigens may be particularly necessary for broadly protective immunization against influenza A virus infections or for candidate vaccines targeting chronic infections and cancer. Here, we tested recombinant MVAs that targeted a model antigen, GFP, to different localizations in infected cells. In vitro characterization demonstrated that GFP accumulated in the nucleus (MVA-nls-GFP), associated with cellular membranes (MVA-myr-GFP) or was equally distributed throughout the cell (MVA-GFP). On vaccination, we found significantly higher levels of GFP-specific CD8(+)T-cells in MVA-myr-GFP-vaccinated BALB/c mice than in those immunized with MVA-GFP or MVA-nls-GFP. Thus, myristoyl modification may be a useful strategy to enhance CD8(+)T-cell responses to MVA-delivered target antigens.
authors: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539, Munich, Germany.
authors: Lisa
authors: L
authors: Marr
authors: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539, Munich, Germany.
authors: Anna-Theresa
authors: AT
authors: Lülf
authors: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539, Munich, Germany.
authors: Astrid
authors: A
authors: Freudenstein
authors: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539, Munich, Germany.
authors: Gerd
authors: G
authors: Sutter
authors: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539, Munich, Germany.
authors: Asisa
authors: A
authors: Volz
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure / Q000821:virology; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000648:ultrastructure; D002642:Chick Embryo; D005229:Fatty Acids, Monounsaturated / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000941:Antigens; D005229:Fatty Acids, Monounsaturated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins; C054211:9-tetradecenoic acid