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.
authors.affiliation: Department of Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. matano@m.u-tokyo.ac.jp
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Igarashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Munehide
authors.initials: M
authors.lastname: Kano
authors.forename: Chie
authors.initials: C
authors.lastname: Sugimoto
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Mori
authors.forename: Akihiro
authors.initials: A
authors.lastname: Iida
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirata
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Takae
authors.initials: T
authors.lastname: Yuasa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nagai
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D015752:Genes, env; D015754:Genes, nef; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines