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Journal of Virology, December 2003, p. 13248-13256, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13248-13256.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Intravenous Inoculation of Replication-Deficient Recombinant Vaccinia Virus DIs Expressing Simian Immunodeficiency Virus Gag Controls Highly Pathogenic Simian-Human Immunodeficiency Virus in Monkeys

Yasuyuki Izumi,1,2 Yasushi Ami,3 Kazuhiro Matsuo,1,2 Kenji Someya,1 Tetsutaro Sata,4 Naoki Yamamoto,1 and Mitsuo Honda1,2*

AIDS Research Center,1 Division of Experimental Animal Research,3 Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640,4 Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012,Japan2

Received 15 July 2003/ Accepted 27 August 2003

To be effective, a vaccine against human immunodeficiency virus type 1 (HIV-1) must induce virus-specific T-cell responses and it must be safe for use in humans. To address these issues, we developed a recombinant vaccinia virus DIs vaccine (rDIsSIVGag), which is nonreplicative in mammalian cells and expresses the full-length gag gene of simian immunodeficiency virus (SIV). Intravenous inoculation of 106 PFU of rDIsSIVGag in cynomologus macaques induced significant levels of gamma interferon (IFN-{gamma}) spot-forming cells (SFC) specific for SIV Gag. Antigen-specific lymphocyte proliferative responses were also induced and were temporally associated with the peak of IFN-{gamma} SFC activity in each macaque. In contrast, macaques immunized with a vector control (rDIsLacZ) showed no significant induction of antigen-specific immune responses. After challenge with a highly pathogenic simian-human immunodeficiency virus (SHIV), CD4+ T lymphocytes were maintained in the peripheral blood and lymphoid tissues of the immunized macaques. The viral set point in plasma was also reduced in these animals, which may be related to the enhancement of virus-specific intracellular IFN-{gamma}+ CD8+ cell numbers and increased antibody titers after SHIV challenge. These results demonstrate that recombinant DIs has potential for use as an HIV/AIDS vaccine.

* Corresponding author. Mailing address: AIDS Research Center, National Institute of Infectious Diseases, 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, December 2003, p. 13248-13256, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13248-13256.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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