|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2009-3-12
|
|
pubmed:abstractText |
Replicon plasmids encoding an alphavirus RNA replicase constitute an alternative to conventional DNA plasmids with promise for DNA vaccination in humans. Replicase activity amplifies the levels of transgene mRNA through a copying process involving double-stranded (ds) RNA intermediates, which contribute to vaccine immunogenicity by activating innate antiviral responses. Toll-like receptor 3 (TLR3) is a dsRNA innate immune receptor expressed by antigen-presenting dendritic cells (DCs). Here, we test the hypothesis that TLR3 is necessary for the immunogenicity of replicon plasmid-based DNA vaccines. We show that mouse CD8 alpha(+) DC phagocytose dying replicon plasmid-transfected cells in vitro and are activated in a TLR3-dependent manner by dsRNA present within those cells. However, we find that cytotoxic T-cell responses to a replicon plasmid intramuscular vaccine are not diminished in the absence of TLR3 in vivo. Our results underscore the potential role of TLR3 in mediating immune activation by dsRNA-bearing replicon plasmid-transfected cells and indicate that other innate sensing pathways can compensate for TLR3 absence in vivo.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-10646851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-10946318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-11070164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-11313828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-11607032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-11715947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-11883692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-12054664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-12383197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-12539043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-12672047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-14502286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-14634101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-15063579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-15208624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-15312142,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-15711573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-1614888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-16625202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-16714379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-16725231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-17350735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-17589544,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-17618271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-17653195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-17892846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-18256672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-18324888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-18591409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-8527474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-8546403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-9348305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19052633-9743526
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8,
http://linkedlifedata.com/resource/pubmed/chemical/CD8 antigen, alpha chain,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Double-Stranded,
http://linkedlifedata.com/resource/pubmed/chemical/TLR3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 3,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
1476-5462
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
16
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
359-66
|
|
pubmed:meshHeading |
pubmed-meshheading:19052633-Animals,
pubmed-meshheading:19052633-Antigens, CD8,
pubmed-meshheading:19052633-Apoptosis,
pubmed-meshheading:19052633-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19052633-Cercopithecus aethiops,
pubmed-meshheading:19052633-Coculture Techniques,
pubmed-meshheading:19052633-Cytotoxicity, Immunologic,
pubmed-meshheading:19052633-Dendritic Cells,
pubmed-meshheading:19052633-Gene Expression,
pubmed-meshheading:19052633-Genes, Transgenic, Suicide,
pubmed-meshheading:19052633-Genetic Vectors,
pubmed-meshheading:19052633-Mice,
pubmed-meshheading:19052633-Mice, Inbred C57BL,
pubmed-meshheading:19052633-Mice, Knockout,
pubmed-meshheading:19052633-Plasmids,
pubmed-meshheading:19052633-RNA, Double-Stranded,
pubmed-meshheading:19052633-Replicon,
pubmed-meshheading:19052633-Spleen,
pubmed-meshheading:19052633-Toll-Like Receptor 3,
pubmed-meshheading:19052633-Transfection,
pubmed-meshheading:19052633-Vaccination,
pubmed-meshheading:19052633-Vaccines, DNA,
pubmed-meshheading:19052633-Vero Cells
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
Role of TLR3 in the immunogenicity of replicon plasmid-based vaccines.
|
|
pubmed:affiliation |
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK. sandra.diebold@kcl.ac.uk
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
