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 Viroljournal_title
Journal of virologyauthors
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 GDdoi
10.1128/JVI.00138-10subject
Has Abstractpub_date
2010-05-01 00:00:00pages
4998-5006issue
10eissn
0022-538Xissn
1098-5514pii
JVI.00138-10journal_volume
84pub_type
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