title: Vaccine-induced CD8+ T cells control AIDS virus replication.
abstract: Developing a vaccine for human immunodeficiency virus (HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus. Most of these elite controllers express the histocompatibility alleles HLA-B*57 or HLA-B*27 (ref. 3). These alleles remain by far the most robust associations with low concentrations of plasma virus, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate Indian rhesus macaques that express Mamu-B*08, an animal model for HLA-B*27-mediated elite control, with three Mamu-B*08-restricted CD8(+) T-cell epitopes, and demonstrate that these vaccinated animals control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 virus. High frequencies of CD8(+) T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon were associated with viral control. Moreover, the frequency of the CD8(+) T-cell response against the Nef RL10 epitope (Nef amino acids 137-146) correlated significantly with reduced acute phase viraemia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8(+) T-cell responses in the control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8(+) T-cell responses can control replication of the AIDS virus.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Mudd
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Martins
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ericsen
authors.forename: Damien C
authors.initials: DC
authors.lastname: Tully
authors.forename: Karen A
authors.initials: KA
authors.lastname: Power
authors.forename: Alex T
authors.initials: AT
authors.lastname: Bean
authors.forename: Shari M
authors.initials: SM
authors.lastname: Piaskowski
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.forename: Aaron
authors.initials: A
authors.lastname: Seese
authors.forename: Adrianne D
authors.initials: AD
authors.lastname: Gladden
authors.forename: Kim L
authors.initials: KL
authors.lastname: Weisgrau
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Furlott
authors.forename: Young-il
authors.initials: YI
authors.lastname: Kim
authors.forename: Marlon G
authors.initials: MG
authors.lastname: Veloso de Santana
authors.forename: Eva
authors.initials: E
authors.lastname: Rakasz
authors.forename: Saverio
authors.initials: S
authors.lastname: Capuano
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Myrna C
authors.initials: MC
authors.lastname: Bonaldo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Galler
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000517:prevention & control; D014779:Virus Replication / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen; D016056:Immunodominant Epitopes; D018449:SAIDS Vaccines