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 Watkins, Yoshiyuki Nagai

Research output: Contribution to journalArticle

180 Citations (Scopus)

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

Fingerprint

AIDS Vaccines
Simian Immunodeficiency Virus
Cytotoxic T-Lymphocytes
Virus Replication
Vaccines
Macaca
Viruses
Sendai virus
Viremia
Major Histocompatibility Complex
Macaca mulatta
Haplotypes
Disease Progression
Chronic Disease
HIV
T-Lymphocytes
Mutation
DNA
Infection

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial. / Matano, Tetsuro; Kobayashi, Masahiro; Igarashi, Hiroko; Takeda, Akiko; Nakamura, Hiromi; Kano, Munehide; Sugimoto, Chie; Mori, Kazuyasu; Iida, Akihiro; Hirata, Takahiro; Hasegawa, Mamoru; Yuasa, Takae; Miyazawa, Masaaki; Takahashi, Yumiko; Yasunami, Michio; Kimura, Akinori; O'Connor, David H.; Watkins, David; Nagai, Yoshiyuki.

In: Journal of Experimental Medicine, Vol. 199, No. 12, 21.06.2004, p. 1709-1718.

Research output: Contribution to journalArticle

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, DH, Watkins, D & Nagai, Y 2004, 'Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial', Journal of Experimental Medicine, vol. 199, no. 12, pp. 1709-1718. https://doi.org/10.1084/jem.20040432
Matano, Tetsuro ; Kobayashi, Masahiro ; Igarashi, Hiroko ; Takeda, Akiko ; Nakamura, Hiromi ; Kano, Munehide ; Sugimoto, Chie ; Mori, Kazuyasu ; Iida, Akihiro ; Hirata, Takahiro ; Hasegawa, Mamoru ; Yuasa, Takae ; Miyazawa, Masaaki ; Takahashi, Yumiko ; Yasunami, Michio ; Kimura, Akinori ; O'Connor, David H. ; Watkins, David ; Nagai, Yoshiyuki. / Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 12. pp. 1709-1718.
@article{90a518d02181464d9f95abd9f92d4870,
title = "Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial",
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.",
keywords = "CD8 T lymphocytes, MHC, Selection, Sendai virus, SIV",
author = "Tetsuro Matano and Masahiro Kobayashi and Hiroko Igarashi and Akiko Takeda and Hiromi Nakamura and Munehide Kano and Chie Sugimoto and Kazuyasu Mori and Akihiro Iida and Takahiro Hirata and Mamoru Hasegawa and Takae Yuasa and Masaaki Miyazawa and Yumiko Takahashi and Michio Yasunami and Akinori Kimura and O'Connor, {David H.} and David Watkins and Yoshiyuki Nagai",
year = "2004",
month = "6",
day = "21",
doi = "10.1084/jem.20040432",
language = "English",
volume = "199",
pages = "1709--1718",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

TY - JOUR

T1 - Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial

AU - Matano, Tetsuro

AU - Kobayashi, Masahiro

AU - Igarashi, Hiroko

AU - Takeda, Akiko

AU - Nakamura, Hiromi

AU - Kano, Munehide

AU - Sugimoto, Chie

AU - Mori, Kazuyasu

AU - Iida, Akihiro

AU - Hirata, Takahiro

AU - Hasegawa, Mamoru

AU - Yuasa, Takae

AU - Miyazawa, Masaaki

AU - Takahashi, Yumiko

AU - Yasunami, Michio

AU - Kimura, Akinori

AU - O'Connor, David H.

AU - Watkins, David

AU - Nagai, Yoshiyuki

PY - 2004/6/21

Y1 - 2004/6/21

N2 - 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.

AB - 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.

KW - CD8 T lymphocytes

KW - MHC

KW - Selection

KW - Sendai virus

KW - SIV

UR - http://www.scopus.com/inward/record.url?scp=3042545965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042545965&partnerID=8YFLogxK

U2 - 10.1084/jem.20040432

DO - 10.1084/jem.20040432

M3 - Article

C2 - 15210746

AN - SCOPUS:3042545965

VL - 199

SP - 1709

EP - 1718

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 12

ER -