rdf:type |
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lifeskim:mentions |
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pubmed:issue |
41
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pubmed:dateCreated |
2009-8-28
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pubmed:abstractText |
Improving vaccine immunogenicity remains a major challenge in the fight against developing country diseases like malaria and AIDS. We describe a novel strategy to identify new DNA vaccine adjuvants. We have screened components of the Toll-like receptor signalling pathways for their ability to activate pro-inflammatory target genes in transient transfection assays and assessed in vivo adjuvant activity by expressing the activators from the DNA backbone of vaccines. We find that a robust increase in the immune response necessitates co-expression of two activators. Accordingly, the combination of tak1 and tram elicits synergistic reporter activation in transient transfection assays. In a mouse model this combination, but not the individual molecules, induced approximately twofold increases in CD8+ T-cell immune responses. These results indicate that optimal immunogenicity may require activation of distinct innate immune signalling pathways. Thus this strategy offers a novel route to the discovery of a new generation of adjuvants.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP kinase kinase kinase 7,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/TIRP protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1873-2518
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pubmed:author |
pubmed-author:BreguMigenaM,
pubmed-author:FurzeJulieJ,
pubmed-author:GilbertSarah CSC,
pubmed-author:GilchristAshleyA,
pubmed-author:GoodmanAnna LAL,
pubmed-author:HillAdrian V SAV,
pubmed-author:Kiss-TothEndreE,
pubmed-author:LarsenKaren ColbjørnKC,
pubmed-author:RollierChristine SCS,
pubmed-author:SoilleuxElizabeth JEJ,
pubmed-author:SpencerAlexandra JAJ,
pubmed-author:WyllieDavid HDH
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pubmed:issnType |
Electronic
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pubmed:day |
18
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pubmed:volume |
27
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
5589-98
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:19646407-Adjuvants, Immunologic,
pubmed-meshheading:19646407-Animals,
pubmed-meshheading:19646407-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19646407-Cell Line,
pubmed-meshheading:19646407-Female,
pubmed-meshheading:19646407-Gene Expression Profiling,
pubmed-meshheading:19646407-Humans,
pubmed-meshheading:19646407-Interferon-gamma,
pubmed-meshheading:19646407-MAP Kinase Kinase Kinases,
pubmed-meshheading:19646407-Macrophages,
pubmed-meshheading:19646407-Mice,
pubmed-meshheading:19646407-Mice, Inbred BALB C,
pubmed-meshheading:19646407-Mice, Inbred C57BL,
pubmed-meshheading:19646407-Receptors, Interleukin,
pubmed-meshheading:19646407-Vaccines, DNA
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pubmed:year |
2009
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pubmed:articleTitle |
Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines.
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pubmed:affiliation |
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom. karen.colbjorn@googlemail.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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