Evidence map›Paper›PMID 19052633›Full record

ArticleGene therapy2009

Role of TLR3 in the immunogenicity of replicon plasmid-based vaccines.

S S Diebold, O Schulz, L Alexopoulou, W W Leitner, R A Flavell, C Reis e Sousa

Abstract read
In one paragraph

Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 3 countries.

S S DieboldImmunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK. sandra.diebold@kcl.ac.uk
O Schulz
L Alexopoulou
W W Leitner
R A Flavell
C Reis e Sousa
Cancer Research UK · GBInserm · FRNational Cancer Institute · USYale University · US

Funding

Cancer Research UK A3598
6 · The paper itself

Abstract

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.

Indexed as

AnimalsApoptosisCD8 AntigensCD8-Positive T-LymphocytesChlorocebus aethiopsCoculture TechniquesCytotoxicity, ImmunologicDendritic CellsGene ExpressionGenes, Transgenic, SuicideGenetic VectorsMiceMice, Inbred C57BLMice, KnockoutPlasmidsRepliconCD8 antigen, alpha chainCD8 AntigensRNA, Double-StrandedTLR3 protein, mouseToll-Like Receptor 3Vaccines, DNA

Identifiers

PMID19052633
PMCPMC2655288
OpenAlexW1997691654

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.