PMID: 15383580Sep 24, 2004Paper

DNA fusion vaccines induce targeted epitope-specific CTLs against minor histocompatibility antigens from a normal or tolerized repertoire

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jason RiceFreda K Stevenson

Abstract

We have designed DNA fusion vaccines able to induce high levels of epitope-specific CD8(+) T cells, using linked CD4(+) T cell help. Such vaccines can activate effective immunity against tumor Ags. To model performance against minor histocompatibility (H) Ags important in allogeneic hemopoietic stem cell transplantation, responses against the H2D(b)-restricted Uty and Smcy male HY epitopes have been investigated. Vaccination of females induced high levels of tetramer-specific, IFN-gamma-producing CD8(+) T cells against each epitope. Vaccines incorporating a single epitope primed effector CTL able to kill male splenocytes in vitro and in vivo, and HY(Db)Uty-specific vaccination accelerated rejection of syngeneic male skin grafts. Priming against either epitope established long-term memory, expandable by injection of male cells. Expanded CD8(+) T cells remained specific for the priming HY epitope, with responses to the second suppressed. To investigate vaccine performance in a tolerized repertoire, male mice were vaccinated with the fusion constructs. Strikingly, this also generated epitope-specific IFN-gamma-producing CD8(+) T cells with cytotoxic function. However, numbers and avidity were lower than in vaccinated females, and ...Continue Reading

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Citations

May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah BuchanJason Rice
Oct 15, 2005·Current Opinion in Oncology·Freda K Stevenson
Sep 5, 2006·The Journal of Biological Chemistry·Hester A DoyleMark J Mamula
Feb 21, 2007·Scandinavian Journal of Immunology·L SteinaaA Gautam
Apr 6, 2007·Expert Review of Vaccines·Shaw-Wei D TsenT-C Wu
Mar 16, 2013·International Journal of Cancer. Journal International Du Cancer·Juan Campos-PerezFreda K Stevenson
Mar 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathan J RobertsonJulian Dyson
Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael J PalmowskiVincenzo Cerundolo
Apr 28, 2006·European Journal of Immunology·Freda K Stevenson, Jason Rice
Jan 8, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna L FurmanskiJulian Dyson
Jan 26, 2008·Nature Reviews. Cancer·Jason RiceFreda K Stevenson
Jun 7, 2011·Cancer Immunology, Immunotherapy : CII·Freda K StevensonChristian H Ottensmeier

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