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dc.contributor.authorKløverpris, Henrik N.en_US
dc.contributor.authorJackson, Akilen_US
dc.contributor.authorHandley, Amandaen_US
dc.contributor.authorHayes, Peteren_US
dc.contributor.authorGilmour, Jillen_US
dc.contributor.authorRiddell, Lynnen_US
dc.contributor.authorChen, Fabianen_US
dc.contributor.authorAtkins, Marken_US
dc.contributor.authorBoffito, Martaen_US
dc.contributor.authorWalker, Bruce D.en_US
dc.contributor.authorAckland, Jimen_US
dc.contributor.authorSullivan, Marken_US
dc.contributor.authorGoulder, Philipen_US
dc.date.accessioned2014-03-10T20:33:08Z
dc.date.issued2013en_US
dc.identifier.citationKløverpris, H. N., A. Jackson, A. Handley, P. Hayes, J. Gilmour, L. Riddell, F. Chen, et al. 2013. “Non-Immunogenicity of Overlapping Gag Peptides Pulsed on Autologous Cells after Vaccination of HIV Infected Individuals.” PLoS ONE 8 (10): e74389. doi:10.1371/journal.pone.0074389. http://dx.doi.org/10.1371/journal.pone.0074389.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11878844
dc.description.abstractBackground: HIV Gag-specific CD4+ and CD8+ T-cell responses are important for HIV immune control. Pulsing overlapping Gag peptides on autologous lymphocytes (OPAL) has proven immunogenic and effective in reducing viral loads in multiple pigtail macaque studies, warranting clinical evaluation. Methodology We performed a phase I, single centre, placebo-controlled, double-blinded and dose-escalating study to evaluate the safety and preliminary immunogenicity of a novel therapeutic vaccine approach ‘OPAL-HIV-Gag(c)’. This vaccine is comprised of 120 15mer peptides, overlapping by 11 amino acids, spanning the HIV Gag C clade sequence proteome, pulsed on white blood cells enriched from whole blood using a closed system, followed by intravenous reinfusion. Patients with undetectable HIV viral loads (<50 copies/ml plasma) on HAART received four administrations at week 0, 4, 8 and 12, and were followed up for 12 weeks post-treatment. Twenty-three people were enrolled in four groups: 12 mg (n = 6), 24 mg (n = 7), 48 mg (n = 2) or matching placebo (n = 8) with 18 immunologically evaluable. T-cell immunogenicity was assessed by IFNγ ELIspot and intracellular cytokine staining (ICS). Results: The OPAL-HIV-Gag(c) peptides were antigenic in vitro in 17/17 subjects. After vaccination with OPAL-HIV-Gag(c), 1/6 subjects at 12 mg and 1/6 subjects at 24 mg dose groups had a 2- and 3-fold increase in ELIspot magnitudes from baseline, respectively, of Gag-specific CD8+ T-cells at week 14, compared to 0/6 subjects in the placebo group. No Gag-specific CD4+ T-cell responses or overall change in Rev, Nef, Tat and CMV specific responses were detected. Marked, transient and self-limiting lymphopenia was observed immediately post-vaccination (4 hours) in OPAL-HIV-Gag(c) but not in placebo recipients, with median fall from 1.72 to 0.67 million lymphocytes/mL for active groups (P<0.001), compared to post-placebo from 1.70 to 1.56 lymphocytes/ml (P = 0.16). Conclusion/Significance Despite strong immunogenicity observed in several Macaca nemestrina studies using this approach, OPAL-HIV-Gag(c) was not significantly immunogenic in humans and improved methods of generating high-frequency Gag-specific T-cell responses are required. Name of Registry ClinicalTrials.gov, Registry number: NCT01123915, URL trial registry database: http://www.clinicaltrials.gov/ct2/results?term=OPAL-HIV-1001&Search=Searchen
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0074389en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790804/pdf/en
dash.licenseLAAen_US
dc.titleNon-Immunogenicity of Overlapping Gag Peptides Pulsed on Autologous Cells after Vaccination of HIV Infected Individualsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorWalker, Bruce D.en_US
dc.date.available2014-03-10T20:33:08Z
dc.identifier.doi10.1371/journal.pone.0074389*
dash.authorsorderedfalse
dash.contributor.affiliatedWalker, Bruce
dc.identifier.orcid0000-0001-6122-9245


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