| Comparison of immunologic assays for detecting immune responses in HIV immunotherapeutic studies: AIDS Clinical Trials Group Trial A5181. | |
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MedLine Citation:
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PMID: 20631337 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study was designed to evaluate which of several T-cell-specific, immune response assays are the most relevant in measuring the key characteristics of an effective immune response to HIV-1. Using 5 HIV-1 antigens as stimulants, we assessed lymphocyte proliferation, supernatant gamma interferon (IFN-gamma) cytokine production (CP), single-cell IFN-gamma production by enzyme-linked immunospot (ELISPOT) assay, with and without Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs), and intracellular cytokine production (ICC) for IFN-gamma and interleukin 2 (IL-2) by flow cytometry. We used these to compare specimens from HIV-1-infected subjects who were virally suppressed with a stable antiretroviral therapy (ART) regimen (group A) with specimens from subjects not on ART but with HIV-1 viremia of <3,000 copies/ml (group B). The lymphocyte proliferation assay (LPA) did not significantly differentiate between the two groups. Using fresh peripheral blood mononuclear cells (PBMCs), the CP and ELISPOT assays for IFN-gamma detected the greatest differences between the two groups, specific for three of the five HIV-1 antigens, whereas significant differences were seen only in response to one antigen when cryopreserved cells were used. The strongest correlations were seen between the CP and ELISPOT assays. The ELISPOT B-LCL assay showed a cell concentration-dependent increase in IFN-gamma production compared to that shown by the standard ELISPOT assay but did not differentiate between the groups. In the ICC assay, greater numbers of IFN-gamma-producing T cells were seen in group B, and little or no detectable IL-2 production was seen in both groups. These studies highlight complexities of immunologic monitoring of T-cell responses in multisite clinical trials in HIV infection and outline considerations for optimizing these efforts. |
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Authors:
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Bernard J C Macatangay; Lu Zheng; Charles R Rinaldo; Alan L Landay; Richard B Pollard; Savita Pahwa; Michael M Lederman; R Pat Bucy |
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Publication Detail:
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Type: Comparative Study; Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-14 |
Journal Detail:
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Title: Clinical and vaccine immunology : CVI Volume: 17 ISSN: 1556-679X ISO Abbreviation: Clin. Vaccine Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-12-08 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 101252125 Medline TA: Clin Vaccine Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1452-9 Citation Subset: IM |
Affiliation:
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Division of Infectious Diseases/HIV/AIDS Unit, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. macatangaybj@upmc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Anti-HIV Agents / therapeutic use Antigens, Viral / diagnostic use Antiretroviral Therapy, Highly Active / methods Cell Proliferation Female Flow Cytometry HIV Infections / drug therapy, immunology*, therapy* HIV-1 / immunology* Humans Immunoassay / methods Immunotherapy / methods* Interferon-gamma / biosynthesis, secretion Interleukin-2 / biosynthesis Leukocytes, Mononuclear / immunology Male Middle Aged Virology / methods* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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AI038858/AI/NIAID NIH HHS; AI069452/AI/NIAID NIH HHS; AI069471/AI/NIAID NIH HHS; AI27675/AI/NIAID NIH HHS; AI54907/AI/NIAID NIH HHS; AI68634/AI/NIAID NIH HHS; AI68638/AI/NIAID NIH HHS; AI69450/AI/NIAID NIH HHS; AI69477/AI/NIAID NIH HHS; AI69494/AI/NIAID NIH HHS; AI69501/AI/NIAID NIH HHS; AI73961/AI/NIAID NIH HHS; RR25780/RR/NCRR NIH HHS; U01AI068636/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Antigens, Viral; 0/Interleukin-2; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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