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Journal of Virology, May 2007, p. 5202-5211, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02881-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Long-Term Control of Simian Immunodeficiency Virus Replication with Central Memory CD4+ T-Cell Preservation after Nonsterile Protection by a Cytotoxic T-Lymphocyte-Based Vaccine{triangledown}

Miki Kawada,1,2 Tetsuo Tsukamoto,1,3 Hiroyuki Yamamoto,1,3 Akiko Takeda,1 Hiroko Igarashi,3 David I. Watkins,4 and Tetsuro Matano1,3,5*

International Research Center for Infectious Diseases, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan,1 Department of Infectious Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan,2 Department of Microbiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan,3 Wisconsin National Primate Research Center, University of Wisconsin—Madison, 555 Science Drive, Madison, Wisconsin 53711,4 AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan5

Received 30 December 2006/ Accepted 25 February 2007

Induction of virus-specific CD8+ cytotoxic T-lymphocyte (CTL) responses is a promising strategy for AIDS vaccine development. However, it has remained unclear if or how long-term viral containment and disease control are attainable by CTL-based nonsterile protection. Here, we present three rhesus macaques that successfully maintained Env-independent vaccine-based control of simian immunodeficiency virus (SIV) mac239 replication without disease progression for more than 3 years. SIV-specific neutralizing antibody induction was inefficient in these controllers. Vaccine-induced Gag-specific CTLs were crucial for the chronic as well as the primary viral control in one of them, whereas those Gag-specific CTL responses became undetectable and CTLs specific for SIV antigens other than Gag, instead, became predominant in the chronic phase in the other two controllers. A transient CD8+ cell depletion experiment 3 years postinfection resulted in transient reappearance of plasma viremia in these two animals, suggesting involvement of the SIV non-Gag-specific CTLs in the chronic SIV control. This sustained, neutralizing antibody-independent viral control was accompanied with preservation of central memory CD4+ T cells in the chronic phase. Our results suggest that prophylactic CTL vaccine-based nonsterile protection can result in long-term viral containment by adapted CTL responses for AIDS prevention.

* 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}m.u-tokyo.ac.jp

{triangledown} Published ahead of print on 7 March 2007.

Journal of Virology, May 2007, p. 5202-5211, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02881-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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