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Journal of Virology, November 2007, p. 11925-11936, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00903-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cross-Priming of Cytotoxic T Cells Dictates Antigen Requisites for Modified Vaccinia Virus Ankara Vector Vaccines ^,

Georg Gasteiger,^1,4, Wolfgang Kastenmuller,^2,4, Ronny Ljapoci,¹ Gerd Sutter,³ and Ingo Drexler^1,2,4*

GSF, Institute of Molecular Virology, 81675 Munich, Germany,¹ Institute of Virology, TUM, Technical University, 81675 Munich, Germany,² Department of Virology, Paul-Ehrlich-Institute, 63225 Langen, Germany,³ Clinical Cooperation Group Antigen-Specific Immunotherapy, GSF, National Research Center for Environment and Health, Neuherberg, and Technical University, Munich, Germany⁴

Received 27 April 2007/ Accepted 6 August 2007

Recombinant vaccines based on modified vaccinia virus Ankara (MVA) have an excellent record concerning safety and immunogenicity and are currently being evaluated in numerous clinical studies for immunotherapy of infectious diseases and cancer. However, knowledge about the biological properties of target antigens to efficiently induce MVA vaccine-mediated immunity in vivo is sparse. Here, we examined distinct antigen presentation pathways and different antigen formulations contained in MVA vaccines for their capability to induce cytotoxic CD8⁺ T-cell (CTL) responses. Strikingly, we found that CTL responses against MVA-produced antigens were dominated by cross-priming in vivo, despite the ability of the virus to efficiently infect professional antigen-presenting cells such as dendritic cells. Moreover, stable mature protein was preferred to preprocessed antigen as the substrate for cross-priming. Our data are essential for improved MVA vaccine design, as they demonstrate the need for optimal adjustment of the target antigen properties to the intrinsic requirements of the delivering vector system.

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* Corresponding author. Mailing address: GSF-Institute for Molecular Virology, Schneckenburgerstr. 8, D-81675 Munich, Germany. Phone: 49-89-4140 7443. Fax: 49-89-4140 7444. E-mail: drexler{at}gsf.de.

Published ahead of print on 15 August 2007.

Supplemental material for this article may be found at http://jvi.asm.org/.

These authors contributed equally to this work.

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Journal of Virology, November 2007, p. 11925-11936, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00903-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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