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Infection and Immunity, April 2003, p. 1748-1754, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1748-1754.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Induction of Protective Immunity to Listeria monocytogenes with Dendritic Cells Retrovirally Transduced with a Cytotoxic T Lymphocyte Epitope Minigene

Yutaro Nakamura,¹ Takafumi Suda,¹ Toshi Nagata,² Taiki Aoshi,² Masato Uchijima,² Atsushi Yoshida,^2, Kingo Chida,^1* Yukio Koide,² and Hirotoshi Nakamura¹

Second Division, Department of Internal Medicine,¹ Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan²

Received 24 July 2002/ Returned for modification 12 September 2002/ Accepted 9 January 2003

In the present study, we developed a cytotoxic T lymphocyte (CTL) epitope minigene-transduced dendritic cell (DC)-based vaccine against Listeria monocytogenes. Murine bone marrow-derived DCs were retrovirally transduced with a minigene for listeriolysin O (LLO) 91-99, a dominant CTL epitope of L. monocytogenes, and were injected into BALB/c mice intravenously. We found that the DC vaccine was capable of generating peptide-specific CD8⁺ T cells exhibiting LLO 91-99-specific cytotoxic activity and gamma interferon production, leading to induction of protective immunity to the bacterium. Furthermore, we demonstrated that the retrovirally transduced DC vaccine was more effective than a CTL epitope peptide-pulsed DC vaccine and a minigene DNA vaccine for eliciting antilisterial immunity. These results provide an alternative strategy in which retrovirally transduced DCs are used to design vaccines against intracellular pathogens.

Editor: S. H. E. Kaufmann

Present address: Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.