DNA vaccination as a tool to identify subdominant CD8 T cell epitopes |
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| Institution: | 1. Department of Immunology, St. Jude’s Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA;2. Department of Virology and Molecular Biology, St. Jude’s Children’s Research Hospital, Memphis, TN 38105, USA;3. Department of Pathology, University of Tennessee, Memphis, TN 38163, USA;1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive MSC 0445, Bethesda, MD 20892-0445, USA;2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0720, USA;1. Department of Urology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan;1. Department of Virology, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark;2. Smittskyddsinstitutet, Stockholm, Sweden;3. Department of Immunology, University of Copenhagen, Copenhagen, Denmark;1. Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA;2. Energy and Resources Group, University of California, Berkeley, California 94720, USA;1. AuRx, Inc., Baltimore, MD 21202, USA;2. Virology/Immunology Laboratories, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 10 S. Pine Street, Baltimore, MD 21201, USA;1. Department of Virology and Molecular Biology, St. Jude Children''s Research Hospital, Memphis, Tennessee, 38105;2. School of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, United Kingdom;3. Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, Fife, KY16 9ST, United Kingdom |
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| Abstract: | DNA vaccination is highly efficient at inducing CD8+ T cell responses in animal models. Here we investigated whether DNA vaccine technology could be exploited to identify subdominant cytotoxic T lymphocytes (CTL) epitopes. Previous studies have shown that the Sendai virus HN protein does not induce a CD8+ T cell response in C57BL/6 mice. Thus, we vaccinated C57BL/6 mice with a DNA vaccine encoding Sendai virus hemagglutinin neuraminidase (HN) protein. The data show that this strategy elicited a potent Db-restricted CD8+ CTL response against at least one subdominant HN-derived epitope. These CTL were able to lyse Sendai virus-infected target cells, demonstrating that the epitope was appropriately processed and present at sufficient levels for T cell recognition. However, these cells did not confer protection against lethal challenge with Sendai virus. These data demonstrate the capacity of DNA vaccine to raise CTL responses to subdominant epitopes, but show that such responses may be limited in their efficacy against non-persistent viruses. |
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