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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2008

Open Access 01-12-2008 | Research

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

Authors: Yuefei Yu, Petra Pilgrim, Juqiang Yan, Wei Zhou, Marjorie Jenkins, Nicoletta Gagliano, Klaus Bumm, Martin Cannon, Aldo Milzani, Isabella Dalle-Donne, W Martin Kast, Everardo Cobos, Maurizio Chiriva-Internati

Published in: Journal of Translational Medicine | Issue 1/2008

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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 T-lymphocyte (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 investigated the efficiency of the CTLs in killing IE1 targeted cells.

Results

A significant MHC Class I-restricted, anti-IE1-specific CTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC) after one, in vitro, stimulation.

Conclusion

In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.
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Metadata
Title
Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells
Authors
Yuefei Yu
Petra Pilgrim
Juqiang Yan
Wei Zhou
Marjorie Jenkins
Nicoletta Gagliano
Klaus Bumm
Martin Cannon
Aldo Milzani
Isabella Dalle-Donne
W Martin Kast
Everardo Cobos
Maurizio Chiriva-Internati
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2008
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-6-56

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