Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.

dc.contributor.author

Freel, SA

dc.contributor.author

Lamoreaux, L

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Chattopadhyay, PK

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Saunders, K

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Zarkowsky, D

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Overman, RG

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Ochsenbauer, C

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Edmonds, TG

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Kappes, JC

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Cunningham, CK

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Denny, TN

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Weinhold, KJ

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Ferrari, G

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Haynes, BF

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Koup, RA

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Graham, BS

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Roederer, M

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Tomaras, GD

dc.date.accessioned

2021-01-04T21:41:42Z

dc.date.available

2021-01-04T21:41:42Z

dc.date.issued

2010-05

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2021-01-04T21:41:41Z

dc.description.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.

dc.identifier

JVI.00138-10

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0022-538X

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1098-5514

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https://hdl.handle.net/10161/21997

dc.language

eng

dc.publisher

American Society for Microbiology

dc.relation.ispartof

Journal of virology

dc.relation.isversionof

10.1128/jvi.00138-10

dc.subject

T-Lymphocyte Subsets

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CD8-Positive T-Lymphocytes

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Humans

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Adenoviridae

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HIV-1

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HIV Infections

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Vaccines, DNA

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AIDS Vaccines

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Immunization, Secondary

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Vaccination

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Flow Cytometry

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Transduction, Genetic

dc.title

Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.

dc.type

Journal article

duke.contributor.orcid

Saunders, K|0000-0001-7399-7954

duke.contributor.orcid

Cunningham, CK|0000-0002-7725-3052

duke.contributor.orcid

Ferrari, G|0000-0001-7747-3349

duke.contributor.orcid

Tomaras, GD|0000-0001-8076-1931

pubs.begin-page

4998

pubs.end-page

5006

pubs.issue

10

pubs.organisational-group

School of Medicine

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Duke Cancer Institute

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Duke Human Vaccine Institute

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Immunology

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Pathology

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Surgery, Surgical Sciences

pubs.organisational-group

Duke

pubs.organisational-group

Institutes and Centers

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Basic Science Departments

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Clinical Science Departments

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Surgery

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Duke Global Health Institute

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Pediatrics, Infectious Diseases

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University Institutes and Centers

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Institutes and Provost's Academic Units

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Pediatrics

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Medicine, Duke Human Vaccine Institute

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Medicine

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Molecular Genetics and Microbiology

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Duke Innovation & Entrepreneurship

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Initiatives

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Staff

pubs.publication-status

Published

pubs.volume

84

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