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International Immunology Advance Access published online on April 20, 2005
International Immunology, doi:10.1093/intimm/dxh249
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received December 3, 2004
Accepted March 3, 2005

Article

Peptide-loaded chimeric influenza virosomes for efficient in vivo induction of cytotoxic T cells

Mario Amacker 1 *, Olivier Engler 2 *, Andreas R. Kammer 1 *, Sonia Vadrucci 3, David Oberholzer 1, Andreas Cerny 4, and Rinaldo Zurbriggen 1*

1 Pevion Biotech Ltd, Rehhagstrasse 79, CH-3018 Bern, Switzerland
2 Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, CH-3010 Bern, Switzerland
3 Department of Biology Institute of Biochemistry, Federal Institute of Technology ETH, Hoenggerberg, CH-8093 Zurich, Switzerland; Present address: Space Biology Group, ETH Technopark, Technoparkstrasse 1, CH-8005 Zurich, Switzerland
4 Dipartimento di Medicina, Ospedale Regionale di Lugano, Ospedale Civico, CH-6900 Lugano, Switzerland

* To whom correspondence should be addressed.
Rinaldo Zurbriggen, E-mail: rinaldo.zurbriggen{at}pevion.com


  Abstract

Virus-specific CD8+ T cells are thought to play an important role in resolving acute hepatitis C virus (HCV) infection as viral clearance has been associated with a strong and sustained CD8+ T cell response. During the chronic state of HCV infection virus-specific T cells have a low frequency and a reduced responsiveness. Based on this, a therapeutic vaccine increasing the frequency of specific T cells is a promising alternative for the treatment of chronic HCV infection. We improved an existing vaccine platform based on immunopotentiating reconstituted influenza virosomes (IRIVs) for efficient delivery of peptide epitopes to the MHC class I antigen presentation pathway. IRIVs are proteoliposomes composed of phospholipids and influenza surface glycoproteins. Due to their fusogenic activity, IRIVs are able to deliver encapsulated macromolecules, e.g. peptides to immunocompetent cells. We developed a novel method based on chimeric virosomes [chimeric immunopotentiating reconstituted influenza virosomes (CIRIVs)] combining the high peptide-encapsulation capacity of liposomes and the fusion activity of virosomes. This new approach resulted in a 30-fold increase of the amount of incorporated soluble peptide compared with current preparation methods. To study the immunogenicity of chimeric virosomes HLA-A2.1 transgenic mice were immunized with CIRIVs containing the HCV Core132 peptide. Core132-CIRIVs efficiently induced specific cytotoxic and IFN{gamma}-producing T cells already with low peptide doses. Vaccine formulations, which include combinations of different HCV-derived CTL epitopes could be used to induce not only a strong but also a multi-specific CTL response, making them potential candidates for therapeutic and maybe prophylactic T cell vaccines in humans.

Keywords: CTL induction; hepatitis C vaccine.

*These authors contributed equally to this study.


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