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Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T Cell responses following HIV-1 recombinant poxvirus vaccination

Wijesundara, Danushka K.; Jackson, Ronald J.; Lidbury, Brett; Parish, Christopher; Quah, Benjamin J. C; Ranasinghe, Charani

Description

Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality...[Show more]

dc.contributor.authorWijesundara, Danushka K.
dc.contributor.authorJackson, Ronald J.
dc.contributor.authorLidbury, Brett
dc.contributor.authorParish, Christopher
dc.contributor.authorQuah, Benjamin J. C
dc.contributor.authorRanasinghe, Charani
dc.date.accessioned2015-10-12T00:29:41Z
dc.date.available2015-10-12T00:29:41Z
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1885/15865
dc.description.abstractQualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.
dc.description.sponsorshipThis work was supported by Project Grants # 1010395 (BQ and CP) and # 525431 (CR), and a Program Grant # 455395 (CP) from the National Health and Medical Research Council of Australia, an Australian Centre for Hepatitis and HIV Virology EOI 2012 grant (CR and RJJ) and a grant from the Gordon and Gretel Bootes Foundation (BQ and CR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format10 pages
dc.publisherPublic Library of Science
dc.rights© 2014 Wijesundara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.sourcePLoS ONE
dc.subjectaids vaccines
dc.subjectanimals
dc.subjectcross reactions
dc.subjectepitopes
dc.subjectfluorescence
dc.subjecthiv infections
dc.subjecthiv-1
dc.subjecthigh-throughput screening assays
dc.subjecthumans
dc.subjectimmunization, secondary
dc.subjectmale
dc.subjectmice
dc.subjectmice, inbred balb c
dc.subjectmicroarray analysis
dc.subjectpoxviridae
dc.subjectpoxviridae infections
dc.subjectt-lymphocytes, cytotoxic
dc.subjectvaccination
dc.subjectvaccines, dna
dc.subjectvaccinia virus
dc.titleUse of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T Cell responses following HIV-1 recombinant poxvirus vaccination
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume9
dcterms.dateAccepted2014-07-18
dc.date.issued2014-08-29
local.identifier.absfor110799
local.identifier.ariespublicationu6800332xPUB235
local.publisher.urlhttps://www.plos.org/
local.type.statusPublished Version
local.contributor.affiliationWijesundara, Danushka, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Immunology and Infectious Disease, The Australian National University
local.contributor.affiliationRanasinghe, Charani, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Immunology and Infectious Disease, The Australian National University
local.contributor.affiliationJackson, Ronald, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Immunology and Infectious Disease, The Australian National University
local.contributor.affiliationLidbury, Brett, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Immunology and Infectious Disease, The Australian National University
local.contributor.affiliationQuah, Ben, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Immunology and Infectious Disease, The Australian National University
dc.relationhttp://purl.org/au-research/grants/nhmrc/1010395
dc.relationhttp://purl.org/au-research/grants/nhmrc/525431
dc.relationhttp://purl.org/au-research/grants/nhmrc/455395
local.identifier.essn1932-6203
local.bibliographicCitation.issue8
local.bibliographicCitation.startpagee105366
local.bibliographicCitation.lastpage10
local.identifier.doi10.1371/journal.pone.0105366
dc.date.updated2015-12-09T08:47:25Z
local.identifier.scopusID2-s2.0-84907536539
local.identifier.thomsonID000341127500046
CollectionsANU Research Publications

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