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Potential of Transfected Muscle Cells to Contribute to DNA Vaccine Immunogenicity¹

Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702

The mechanism(s) by which DNA vaccines trigger the activation of Ag-specific T cells is incompletely understood. A series of in vivo and in vitro experiments indicates plasmid transfection stimulates muscle cells to up-regulate expression of MHC class I and costimulatory molecules and to produce multiple cytokines and chemokines. Transfected muscle cells gain the ability to directly present Ag to CD8 T cells through an IFN-regulatory factor 3-dependent process. These findings suggest that transfected muscle cells at the site of DNA vaccination may contribute to the magnitude and/or duration of the immune response initiated by professional APCs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Food and Drug Administration at large.

² Current address: Department of Respiratory and Infections Disease, Tohoku University School of Medicine, Sendai, Japan.

³ Address correspondence and reprint requests to Dr. Dennis M. Klinman, Building 567, Room 205, National Cancer Institute, National Institutes of Health, Frederick, MD 21702. E-mail address: klinmand{at}mail.nih.gov

⁴ Abbreviations used in this paper: DC, dendritic cell; RNAi, RNA interference; siRNA, small-interfering RNA; IRF3, IFN-regulatory factor 3; pOVA, OVA-encoding plasmid; LMP, low m.w. protein; IP-10, IFN--inducible protein 10.