title: 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.
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.
authors.affiliation: 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.
authors.forename: Miki
authors.initials: M
authors.lastname: Kawada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Igarashi
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005434:Flow Cytometry; D007156:Immunologic Memory; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D009500:Neutralization Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000956:Antigens, Viral