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.

journal_name

J Virol

journal_title

Journal of virology

authors

Freel SA,Lamoreaux L,Chattopadhyay PK,Saunders K,Zarkowsky D,Overman RG,Ochsenbauer C,Edmonds TG,Kappes JC,Cunningham CK,Denny TN,Weinhold KJ,Ferrari G,Haynes BF,Koup RA,Graham BS,Roederer M,Tomaras GD

doi

10.1128/JVI.00138-10

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

4998-5006

issue

10

eissn

0022-538X

issn

1098-5514

pii

JVI.00138-10

journal_volume

84

pub_type

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