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Journal of Virology, March 2004, p. 2255-2264, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2255-2264.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Expansion of Protective CD8+ T-Cell Responses Driven by Recombinant Cytomegaloviruses

Urs Karrer,1* Markus Wagner,2,{dagger} Sophie Sierro,1 Annette Oxenius,1 Hartmut Hengel,3 Tilman Dumrese,4 Stefan Freigang,4 Ulrich H. Koszinowski,2 Rodney E. Phillips,1 and Paul Klenerman1*

Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom,1 Department of Virology, Max von Pettenkofer Institute, 80336 Munich,2 Department of Virology, Robert Koch-Institute, 13353 Berlin, Germany,3 Department of Pathology, Institute for Experimental Immunology, 8091 Zürich, Switzerland4

Received 21 May 2003/ Accepted 21 November 2003

CD8+ T cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus, and cytomegalovirus (CMV). In most infections, large CD8+-T-cell populations are induced early but then contract and are maintained thereafter at lower levels. In contrast, CD8+ T cells specific for murine CMV (MCMV) have been shown to gradually accumulate after resolution of primary infection. This unique behavior is restricted to certain epitopes, including an immunodominant epitope derived from the immediate-early 1 (IE1) gene product. To explore the mechanism behind this further, we measured CD8+-T-cell-mediated immunity induced by recombinant MCMV-expressing epitopes derived from influenza A virus or lymphocytic choriomeningitis virus placed under the control of an IE promoter. We observed that virus-specific CD8+-T-cell populations were induced and that these expanded gradually over time. Importantly, these CD8+ T cells provided long-term protection against challenge without boosting. These results demonstrate a unique pattern of accumulating T cells, which provide long-lasting immune protection, that is independent of the initial immunodominance of the epitope and indicates the potential of T-cell-inducing vaccines based on persistent vectors.

* Corresponding author. Mailing address for P. Klenerman: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Rd., Oxford OX1 3SY, United Kingdom. Phone: 44(0)1865-281230. Fax: 44(0)1865-281890. E-mail: klener{at}enterprise.molbiol.ox.ac.uk. Mailing address for U. Karrer: Department of Medicine, Division of Infectious Diseases, University Hospital of Zürich, Rämistrasse 100, 8091 Zürich, Switzerland. Phone: 41 1 255 3322. Fax: 41 1 255 4499. E-mail: urs.karrer{at}usz.ch.

{dagger} Present address: Department of Pathology, Harvard Medical School, Boston, MA 02115.

Journal of Virology, March 2004, p. 2255-2264, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2255-2264.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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