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Immune-mediated destruction of transfected myocytes following DNA vaccination occurs via multiple mechanisms

Gene Therapy volume 8, pages 1395–1400 (2001)Cite this article

Abstract

The delivery of antigenic proteins in the context of a DNA vaccine leads to the intracellular synthesis of antigen and the induction of both humoral and cellular immune responses. Subsequent to immune activation, any transfected cell expressing the immunogenic protein should, by the rules of immunology, become a legitimate target for removal by immune-mediated mechanisms. Herein, we have used an indirect assay of myocyte integrity following intra-muscular (i.m.) delivery of a DNA vaccine, in mice with various immune deficiencies, to determine which immunological mechanisms may be involved in destruction of antigen-expressing cells. We demonstrate that destruction of antigen-expressing myocytes following i.m. injection of a DNA vaccine is dependent on major histocompatability complex (MHC) class II restricted CD4+ T cell activation, but is not mediated solely by MHC I-restricted or perforin-mediated lysis and appears to have a component that is antibody-mediated. Although we studied myocytes, the results likely represent what happens to any transfected cell expressing a foreign antigen. This study underscores the ability of DNA vaccines at inducing antigen-specific immune responses that include a number of effector mechanisms. From the perspective of gene therapy, this study highlights the significance of immune activation when considering strategies where maintenance of therapeutic gene expression is desired. Gene Therapy (2001) 8, 1395–1400.

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Acknowledgements

We wish to thank Jocelyn Chandler, Brian Avery, George Condruit, and Chandimal Nicholas for their excellent technical support. This work was supported by a grant from the Medical Research Council of Canada to HLP. PJ Payette is a recipient of an Ontario Graduate Student Award and HL Davis is the recipient of an Ontario Ministry of Health Career Scientist Award.

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Authors and Affiliations

  1. Loeb Health Research Institute, Ottawa, Canada

    PJ Payette & HL Davis

  2. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Canada

    PJ Payette & HL Davis

  3. Coley Pharmaceutical Group Inc., Wellesley, MA, USA

    RD Weeratna, MJ McCluskie & HL Davis

  4. Faculty of Health Sciences, University of Ottawa, Canada

    HL Davis

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  1. PJ Payette
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  2. RD Weeratna
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  4. HL Davis
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Payette, P., Weeratna, R., McCluskie, M. et al. Immune-mediated destruction of transfected myocytes following DNA vaccination occurs via multiple mechanisms. Gene Ther 8, 1395–1400 (2001). https://doi.org/10.1038/sj.gt.3301534

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