Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial

Tetsuro Matano, Masahiro Kobayashi, Hiroko Igarashi, Akiko Takeda, Hiromi Nakamura, Munehide Kano, Chie Sugimoto, Kazuyasu Mori, Akihiro Iida, Takahiro Hirata, Mamoru Hasegawa, Takae Yuasa, Masaaki Miyazawa, Yumiko Takahashi, Michio Yasunami, Akinori Kimura, David H. O'Connor, David I. Watkins, Yoshiyuki Nagai

Research output: Contribution to journalArticle

182 Scopus citations

Abstract

Recently, encouraging AIDS vaccine trials in macaques have implicated cytotoxic T lymphocytes (CTLs) in the control of the simian human immunodeficiency virus SHIV89.6P that induces acute CD4+T cell depletion. However, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (SIVs) that induce chronic disease progression. Indeed, it has remained unclear if vaccine-induced CTL can control SIV replication. Here, we show evidence suggesting that vaccine-induced CTLs control SIVmac239 replication in rhesus macaques. Eight macaques vaccinated with DNA-prime/Gag-expressing Sendai virus vector boost were challenged intravenously with SIVmac239. Five of the vaccinees controlled viral replication and had undetectable plasma viremia after 5 wk of infection. CTLs from all of these five macaques rapidly selected for escape mutations in Gag, indicating that vaccine-induced CTLs successfully contained replication of the challenge virus. Interestingly, analysis of the escape variant selected in three vaccinees that share a major histocompatibility complex class I haplotype revealed that the escape variant virus was at a replicative disadvantage compared with SIVmac239. These findings suggested that the vaccine-induced CTLs had "crippled" the challenge virus. Our results indicate that vaccine induction of highly effective CTLs can result in the containment of replication of a highly pathogenic immunodeficiency virus.

Original languageEnglish (US)
Pages (from-to)1709-1718
Number of pages10
JournalJournal of Experimental Medicine
Volume199
Issue number12
DOIs
StatePublished - Jun 21 2004

Keywords

  • CD8 T lymphocytes
  • MHC
  • Selection
  • Sendai virus
  • SIV

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Matano, T., Kobayashi, M., Igarashi, H., Takeda, A., Nakamura, H., Kano, M., Sugimoto, C., Mori, K., Iida, A., Hirata, T., Hasegawa, M., Yuasa, T., Miyazawa, M., Takahashi, Y., Yasunami, M., Kimura, A., O'Connor, D. H., Watkins, D. I., & Nagai, Y. (2004). Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial. Journal of Experimental Medicine, 199(12), 1709-1718. https://doi.org/10.1084/jem.20040432