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Journal of Virology, September 2009, p. 9339-9346, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.01120-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Impact of Cytotoxic-T-Lymphocyte Memory Induction without Virus-Specific CD4+ T-Cell Help on Control of a Simian Immunodeficiency Virus Challenge in Rhesus Macaques{triangledown}

Tetsuo Tsukamoto,1 Akiko Takeda,1 Takuya Yamamoto,2 Hiroyuki Yamamoto,1 Miki Kawada,1 and Tetsuro Matano1,3,4*

International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan,1 Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan,2 AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan,3 Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba 305-0843, Japan4

Received 2 June 2009/ Accepted 29 June 2009

Despite many efforts to develop AIDS vaccines eliciting virus-specific T-cell responses, whether induction of these memory T cells by vaccination before human immunodeficiency virus (HIV) exposure can actually contribute to effective T-cell responses postinfection remains unclear. In particular, induction of HIV-specific memory CD4+ T cells may increase the target cell pool for HIV infection because the virus preferentially infects HIV-specific CD4+ T cells. However, virus-specific CD4+ helper T-cell responses are thought to be important for functional CD8+ cytotoxic-T-lymphocyte (CTL) induction in HIV infection, and it has remained unknown whether HIV-specific memory CD8+ T cells induced by vaccination without HIV-specific CD4+ T-cell help can exert effective responses after virus exposure. Here we show the impact of CD8+ T-cell memory induction without virus-specific CD4+ T-cell help on the control of a simian immunodeficiency virus (SIV) challenge in rhesus macaques. We developed a prophylactic vaccine by using a Sendai virus (SeV) vector expressing a single SIV Gag241-249 CTL epitope fused with enhanced green fluorescent protein (EGFP). Vaccination resulted in induction of SeV-EGFP-specific CD4+ T-cell and Gag241-249-specific CD8+ T-cell responses. After a SIV challenge, the vaccinees showed dominant Gag241-249-specific CD8+ T-cell responses with higher effector memory frequencies in the acute phase and exhibited significantly reduced viral loads. These results demonstrate that virus-specific memory CD8+ T cells induced by vaccination without virus-specific CD4+ T-cell help could indeed facilitate SIV control after virus exposure, indicating the benefit of prophylactic vaccination eliciting virus-specific CTL memory with non-virus-specific CD4+ T-cell responses for HIV control.

* Corresponding author. Mailing address: International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-6409-2078. Fax: 81-3-6409-2076. E-mail: matano{at}ims.u-tokyo.ac.jp

{triangledown} Published ahead of print on 8 July 2009.

Journal of Virology, September 2009, p. 9339-9346, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.01120-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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