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Journal of Virology, October 2005, p. 12871-12879, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12871-12879.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Priming-Boosting Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and a Nonreplicating Vaccinia Virus Recombinant Leads to Long-Lasting and Effective Immunity

Yasushi Ami,1 Yasuyuki Izumi,2 Kazuhiro Matsuo,2 Kenji Someya,2 Masaru Kanekiyo,2 Shigeo Horibata,2 Naoto Yoshino,4 Koji Sakai,2 Katsuaki Shinohara,3 Sohkichi Matsumoto,5 Takeshi Yamada,6 Shudo Yamazaki,2 Naoki Yamamoto,2 and Mitsuo Honda2*

Division of Experimental Animal Research,1 AIDS Research Center,2 Division of Biosafety Control and Research, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan,3 Department of Microbiology and Immunology, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka, Iwate 020-8505, Japan,4 Department of Host Defense, Graduate School of Medicine, Osaka City University, Osaka, Osaka 545-8585, Japan,5 Department of Bacteriology, School of Dentistry, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan6

Received 29 April 2005/ Accepted 22 July 2005

Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-{gamma}) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-{gamma} activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

* Corresponding author. Mailing address: AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111, ext. 2737. Fax: 81-3-5285-1183. E-mail: mhonda{at}nih.go.jp.

Journal of Virology, October 2005, p. 12871-12879, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12871-12879.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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