This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kawada, M.
Right arrow Articles by Matano, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kawada, M.
Right arrow Articles by Matano, T.

 Previous Article  |  Next Article 

Journal of Virology, October 2008, p. 10199-10206, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01103-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Gag-Specific Cytotoxic T-Lymphocyte-Based Control of Primary Simian Immunodeficiency Virus Replication in a Vaccine Trial {triangledown}

Miki Kawada,1,2 Tetsuo Tsukamoto,1 Hiroyuki Yamamoto,1 Nami Iwamoto,1 Kyoko Kurihara,1 Akiko Takeda,1 Chikaya Moriya,1 Hiroaki Takeuchi,1 Hirofumi Akari,3 and Tetsuro Matano1,3,4*

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,1 Japanese Foundation for AIDS Prevention, 1-3-12 Misaki-Cho, Chiyoda-Ku, Tokyo 101-0061, Japan,2 Tsukuba Primate Research Center, National Institute of Biomedical Innovation, 1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan,3 AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-Ku, Tokyo 162-8640, Japan4

Received 26 May 2008/ Accepted 21 July 2008

Gag-specific cytotoxic T lymphocytes (CTLs) exert strong suppressive pressure on human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. However, it has remained unclear whether they can actually contain primary viral replication. Recent trials of prophylactic vaccines inducing virus-specific T-cell responses have indicated their potential to confer resistance against primary SIV replication in rhesus macaques, while the immunological determinant for this vaccine-based viral control has not been elucidated thus far. Here we present evidence implicating Gag-specific CTLs as responsible for the vaccine-based primary SIV control. Prophylactic vaccination using a Gag-expressing Sendai virus vector resulted in containment of SIVmac239 challenge in all rhesus macaques possessing the major histocompatibility complex (MHC) haplotype 90-120-Ia. In contrast, 90-120-Ia-positive vaccinees failed to contain SIVs carrying multiple gag CTL escape mutations that had been selected, at the cost of viral fitness, in SIVmac239-infected 90-120-Ia-positive macaques. These results show that Gag-specific CTL responses do play a crucial role in the control of wild-type SIVmac239 replication in vaccinees. This study implies the possibility of Gag-specific CTL-based primary HIV containment by prophylactic vaccination, although it also suggests that CTL-based AIDS vaccine efficacy may be abrogated in viral transmission between MHC-matched individuals.

* 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 30 July 2008.

Journal of Virology, October 2008, p. 10199-10206, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01103-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Arrode-Bruses, G., Sheffer, D., Hegde, R., Dhillon, S., Liu, Z., Villinger, F., Narayan, O., Chebloune, Y. (2010). Characterization of T-Cell Responses in Macaques Immunized with a Single Dose of HIV DNA Vaccine. J. Virol. 84: 1243-1253 [Abstract] [Full Text]  
  • Haut, L. H., Ertl, H. C. J. (2009). Obstacles to the successful development of an efficacious T cell-inducing HIV-1 vaccine. J. Leukoc. Biol. 86: 779-793 [Abstract] [Full Text]  
  • Tsukamoto, T., Takeda, A., Yamamoto, T., Yamamoto, H., Kawada, M., Matano, T. (2009). 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. J. Virol. 83: 9339-9346 [Abstract] [Full Text]  
  • Yamamoto, T., Iwamoto, N., Yamamoto, H., Tsukamoto, T., Kuwano, T., Takeda, A., Kawada, M., Tsunetsugu-Yokota, Y., Matano, T. (2009). Polyfunctional CD4+ T-Cell Induction in Neutralizing Antibody-Triggered Control of Simian Immunodeficiency Virus Infection. J. Virol. 83: 5514-5524 [Abstract] [Full Text]  
  • Crawford, H., Lumm, W., Leslie, A., Schaefer, M., Boeras, D., Prado, J. G., Tang, J., Farmer, P., Ndung'u, T., Lakhi, S., Gilmour, J., Goepfert, P., Walker, B. D., Kaslow, R., Mulenga, J., Allen, S., Goulder, P. J.R., Hunter, E. (2009). Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients. JEM 206: 909-921 [Abstract] [Full Text]  
  • Kong, W.-P., Wu, L., Wallstrom, T. C., Fischer, W., Yang, Z.-Y., Ko, S.-Y., Letvin, N. L., Haynes, B. F., Hahn, B. H., Korber, B., Nabel, G. J. (2009). Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination. J. Virol. 83: 2201-2215 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»