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The Journal of Immunology, 2007, 179, 2126-2133
Copyright © 2007 by The American Association of Immunologists, Inc.

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In Vivo Antigen Stability Affects DNA Vaccine Immunogenicity

Adriaan D. Bins1, Monika C. Wolkers1,2, Marly D. van den Boom, John B. A. G. Haanen and Ton N. M. Schumacher3

Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

The factors that determine the immunogenicity of Ags encoded by viral vaccines or DNA vaccines in vivo are largely unknown. Depending on whether T cell induction occurs via direct presentation of vaccine-encoded epitopes or via one of the different proposed pathways for Ag cross-presentation, the effect of intracellular Ag stability on immunogenicity may possibly vary. However, the influence of Ag stability on CD8+ T cell induction has not been addressed in clinically relevant vaccine models, nor has the accumulation of vaccine-encoded Ags been monitored in vivo. In this study, we describe the relationship between in vivo Ag stability and immunogenicity of DNA vaccine-encoded Ags. We show that in vivo accumulation of DNA vaccine-encoded Ags is required for the efficient induction of CD8+ T cell responses. These data suggest that many of the currently used transgene designs in DNA vaccination trials may be suboptimal, and that one should either use pathogen-derived or tumor-associated Ags that are intrinsically stable, or should increase the stability of vaccine-encoded Ags by genetic engineering.

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 A.D.B. and M.C.W. contributed equally to this work.

2 Current address: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037.

3 Address correspondence and reprint requests to Dr. Ton N. M. Schumacher, Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. E-mail address: t.schumacher{at}nki.nl

4 Abbreviations used in this paper: NP, nucleoprotein; DLN, draining lymph node; i.d., intradermal; Ub, ubiquitin.


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The JI 2007 179: 2033-2034. [Full Text]  






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