title: Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.
abstract: Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8(+) T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8(+) T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8(+) T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8(+) T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8(+) T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1beta (MIP-1beta) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8(+) T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8(+) T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.
authors.affiliation: Duke University Human Vaccine Institute, Departments of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Freel
authors.forename: Laurie
authors.initials: L
authors.lastname: Lamoreaux
authors.forename: Pratip K
authors.initials: PK
authors.lastname: Chattopadhyay
authors.forename: Kevin
authors.initials: K
authors.lastname: Saunders
authors.forename: David
authors.initials: D
authors.lastname: Zarkowsky
authors.forename: R Glenn
authors.initials: RG
authors.lastname: Overman
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer
authors.forename: Tara G
authors.initials: TG
authors.lastname: Edmonds
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014161:Transduction, Genetic; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA