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

Miki Kawada, Tetsuo Tsukamoto, Hiroyuki Yamamoto, Akiko Takeda, Hiroko Igarashi, David Watkins, Tetsuro Matano

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5202-5211
Number of pages10
JournalJournal of Virology
Volume81
Issue number10
DOIs
StatePublished - May 1 2007
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
Virus Replication
virus replication
Vaccines
T-lymphocytes
vaccines
T-Lymphocytes
controllers
Neutralizing Antibodies
neutralizing antibodies
gag Gene Products
Virus Activation
AIDS Vaccines
Viremia
viremia
vaccine development
Virus Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Kawada, Miki; Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Takeda, Akiko; Igarashi, Hiroko; Watkins, David; Matano, Tetsuro.

In: Journal of Virology, Vol. 81, No. 10, 01.05.2007, p. 5202-5211.

Research output: Contribution to journalArticle

Kawada, Miki ; Tsukamoto, Tetsuo ; Yamamoto, Hiroyuki ; Takeda, Akiko ; Igarashi, Hiroko ; Watkins, David ; Matano, Tetsuro. / 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. In: Journal of Virology. 2007 ; Vol. 81, No. 10. pp. 5202-5211.
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