| Low frequency of amino acid alterations following therapeutic immunization with HIV-1 Gag p24-like peptides. | |
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MedLine Citation:
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PMID: 20935558 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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OBJECTIVES: In chronic HIV-1 infection, the efficacy of a cellular immune response may decline if the virus evolves into variants not recognized by host immune response. The aim of this study was to explore HIV-1 immune escape mutations imposed by therapeutic immunization by investigating sequence variations that might contribute to relapse of viremia in an immunized, HIV-1-infected cohort. DESIGN: We have previously immunized HIV-1-infected individuals on antiretroviral therapy (ART) with a mixture of four short peptides (Vacc-4x) corresponding to p24. Long postimmunization periods without ART allowed longitudinal sequence studies of regions corresponding to Vacc-4x. METHODS: Regions of gag p24 including the locations of the Vacc-4x peptides, were sequenced before start of ART, and after postimmunization ART stop (n = 27). Rates and locations of amino acid substitutions were then related to peptide-specific T-cell responses and known epitopes presented by Vacc-4x. RESULTS: The overall rate of amino acid substitutions was low during 35 months (median) of postimmunization viremia, with similar rates of substitution within the regions corresponding to Vacc-4x peptides and other p24 regions despite durable Vacc-4x-specific T-cell responses. Postimmunization amino acid substitutions within Vacc-4x regions were detected in only six patients, and only two of them had measurable T-cell responses against the relevant peptide. CONCLUSIONS: The results suggested low prevalence of evolutionary selection of p24 despite new and long-lasting Vacc-4x-specific T-cell responses. The conserved Vacc-4x sequences might therefore be particularly suited for therapeutic immunization. Generally, studies of longitudinal sequence variations after immunization might be valuable when assessing immune escape in HIV vaccine trials. |
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Authors:
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Anne-Marte B Kran; Tom Oystein Jonassen; Maja A Sommerfelt; Gunilla Løvgården; Birger Sørensen; Dag Kvale |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: AIDS (London, England) Volume: 24 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8710219 Medline TA: AIDS Country: England |
Other Details:
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Languages: eng Pagination: 2609-18 Citation Subset: IM; X |
Affiliation:
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Department of Infectious Diseases, Oslo University Hospital, Ullevål, Norway. a.m.b.kran@medisin.uio.no |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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