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Infection and Immunity, November 2005, p. 7356-7365, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7356-7365.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Immune Responses against a Single CD8+-T-Cell Epitope Induced by Virus Vector Vaccination Can Successfully Control Trypanosoma cruzi Infection

Yasushi Miyahira,1,2* Yasuhiro Takashima,3 Seiki Kobayashi,4 Yasunobu Matsumoto,3 Tsutomu Takeuchi,4 Mutsuko Ohyanagi-Hara,1 Ayako Yoshida,2 Akihiko Ohwada,5 Hisaya Akiba,6 Hideo Yagita,6 Ko Okumura,1,6 and Hideoki Ogawa1,7

Atopy Research Center,1 Department of Parasitology,2 Department of Respiratory Medicine,5 Department of Immunology,6 Department of Dermatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan,7 Laboratory of Global Animal Resource Science, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan,3 Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan4

Received 2 June 2005/ Returned for modification 9 July 2005/ Accepted 7 August 2005

In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NF{kappa}B (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.

* Corresponding author. Mailing address: Atopy Research Center, Department of Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Phone: 81-3-5802-1591. Fax: 81-3-3813-5512. E-mail: miyahira{at}med.juntendo.ac.jp.

Editor: W. A. Petri, Jr.

Infection and Immunity, November 2005, p. 7356-7365, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7356-7365.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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