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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens / chemistry*
-
Antigens / genetics
-
Antigens / immunology
-
CD8-Positive T-Lymphocytes / drug effects
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / ultrastructure
-
CD8-Positive T-Lymphocytes / virology
-
Cell Line
-
Cell Nucleus / immunology
-
Cell Nucleus / ultrastructure
-
Chick Embryo
-
Fatty Acids, Monounsaturated / immunology
-
Fatty Acids, Monounsaturated / metabolism
-
Female
-
Fibroblasts / immunology
-
Fibroblasts / virology
-
Green Fluorescent Proteins / administration & dosage
-
Green Fluorescent Proteins / chemistry
-
Green Fluorescent Proteins / immunology*
-
Immunity, Cellular / drug effects
-
Lymphocyte Count
-
Mice
-
Mice, Inbred BALB C
-
NIH 3T3 Cells
-
Protein Processing, Post-Translational / immunology*
-
Vaccination
-
Vaccines, Synthetic
-
Vaccinia virus / genetics*
-
Vaccinia virus / immunology
-
Viral Vaccines / administration & dosage
-
Viral Vaccines / immunology*
Substances
-
Antigens
-
Fatty Acids, Monounsaturated
-
Vaccines, Synthetic
-
Viral Vaccines
-
Green Fluorescent Proteins
-
9-tetradecenoic acid