A liposomal peptide vaccine inducing CD8+ T cells in HLA-A2.1 transgenic mice, which recognize human cells encoding hepatitis C virus (HCV) proteins
| Autor: | Andreas Cerny, Olivier B. Engler, Darius Moradpour, Benno Wölk, Wen Juan Dai, Reto A. Schwendener, Thomas Brunner, Werner J. Pichler |
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| Přispěvatelé: | University of Zurich |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
3400 General Veterinary
T cell Mice Transgenic Hepacivirus CD8-Positive T-Lymphocytes Hepatitis Animal Biology Epitope Virus Cell Line Mice Immune system 2400 General Immunology and Microbiology ddc:570 HLA-A2 Antigen Vaccinia medicine Animals Humans Cytotoxic T cell Vaccines Synthetic Peptide immunisation General Veterinary General Immunology and Microbiology Hepatitis C virus 10061 Institute of Molecular Cancer Research Public Health Environmental and Occupational Health 2739 Public Health Environmental and Occupational Health 2725 Infectious Diseases Virology Molecular biology Infectious Diseases medicine.anatomical_structure Cell culture 1313 Molecular Medicine Vaccines Subunit Liposomes Peptide vaccine 570 Life sciences biology Molecular Medicine CD8 |
| Popis: | Virus specific T cell responses play an important role in resolving acute hepatitis C virus (HCV) infections. Using the HLA-A2.1 transgenic mouse model we investigated the potential of a liposomal peptide vaccine to prime a CD8(+) T cell response against 10 different HCV epitopes, relevant for human applications. We were able to demonstrate the induction of strong cytotoxic T cell responses and high numbers of IFN-gamma-secreting cells, which persisted at high levels for at least 3 months. Co-integrating CpG oligonucleotides into liposomes further increased the number of IFN-gamma-secreting cells by 2-10-fold for most epitopes tested. The frequency of specific cells was further analysed with chimeric A2 tetramers bearing the NS31073-1081 epitope and was estimated at 2-23% of the CD8(+) T cell population. Importantly, mouse effector cells, specific for this epitope, were also capable of lysing a human target cell line expressing HCV proteins. This finding and the specific protection observed in challenge experiments with recombinant vaccinia virus expressing HCV sequences emphasise the biological relevance of the vaccine-induced immune response. In conclusion, such liposome formulations represent a safe and promising strategy to stimulate the CD8(+) T cell against HCV. |
| Databáze: | OpenAIRE |
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