Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells

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BioMed Central

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Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells Yuefei Yu†1, Petra Pilgrim†1, Juqiang Yan1, Wei Zhou1, Marjorie Jenkins2, Nicoletta Gagliano1,3, Klaus Bumm1,4, Martin Cannon5, Aldo Milzani6, Isabella Dalle-Donne6, W Martin Kast7,8, Everardo Cobos1 and Maurizio Chiriva-Internati*1,8 Address: 1Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA, 2Departments of Internal Medicine and Obstetrics & Gynecology, and the Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, USA, 3Department of Human Morphology, University of Milan, Italy, 4Department of Otorhinolaryngology, Head & Neck Surgery, University of Erlangen-Nuremberg, FAU Medical School, Erlangen, Germany, 5Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, AR, USA, 6Department of Biology, University of Milan, Milan, Italy, 7Departments of Molecular Microbiology & Immunology and Obstetrics & Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA and 8Kiromic, Inc., Lubbock, TX, USA Email: Yuefei Yu - [email protected]; Petra Pilgrim - [email protected]; Juqiang Yan - [email protected]; Wei Zhou - [email protected]; Marjorie Jenkins - [email protected]; Nicoletta Gagliano - [email protected]; Klaus Bumm - [email protected]; Martin Cannon - [email protected]; Aldo Milzani - [email protected]; Isabella DalleDonne - [email protected]; W Martin Kast - [email protected]; Everardo Cobos - [email protected]; Maurizio ChirivaInternati* - [email protected] * Corresponding author †Equal contributors

Published: 5 October 2008 Journal of Translational Medicine 2008, 6:56

doi:10.1186/1479-5876-6-56

Received: 31 May 2008 Accepted: 5 October 2008

This article is available from: http://www.translational-medicine.com/content/6/1/56 © 2008 Yu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates in vitro, significant and rapid cytotoxic Tlymphocyte (CTL) responses against viral antigens. Methods: We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV) gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1), expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then inv