Evidence map›Paper›PMID 16725231›Full record

ArticleVaccine2006

Type I Interferons are essential for the efficacy of replicase-based DNA vaccines.

Wolfgang W Leitner, Elke S Bergmann-Leitner, Leroy N Hwang, Nicholas P Restifo

Open access · greenAbstract read
In one paragraph

Article in Vaccine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

23 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. DNA and mRNA vaccination against allergies.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2018
    Review
  6. Article
  7. Article
  8. Article
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  10. Article
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  18. Article
  19. DNA vaccines: developing new strategies against cancer.Journal of biomedicine & biotechnology · 2010
    Review
  20. Article
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

4 authors at 4 institutions in 1 country.

Wolfgang W LeitnerClinical Research Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wolfgang_leitner@nih.gov
Elke S Bergmann-Leitner
Leroy N Hwang
Nicholas P Restifo
National Cancer Institute · USNational Institutes of Health · USNational Institutes of Health Clinical Center · USWalter Reed Army Institute of Research · US

Funding

Building on the success of the adoptive immunotherapy of cancerZ01BC010763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RESTIFO, NICHOLAS P · 2006 to 2008
$6.4M
RECOMBINANT AND SYNTHETIC ANTI-CANCER VACCINESZ01SC006670 · SC · CLINICAL SCIENCES · PI RESTIFO, NICHOLAS P · 1996 to 2005
–
Intramural NIH HHS Z01 BC010763Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

The immunogenicity and efficacy of nucleic acid vaccines can be greatly enhanced when antigen production is under the control of an alphaviral replicase enzyme. However, replicase-mediated mRNA overproduction does not necessarily result in enhanced antigen level. Instead, the strong adaptive immune response of alphavirus replicon-based vectors is due to their production of double-stranded RNA (dsRNA) intermediates, which trigger innate immunity. Because viral infections are known to trigger innate immune responses that lead to the rapid production of Type I Interferons (IFNs), namely IFN-alpha and IFN-beta, we investigated the role of Type I IFNs in the enhanced immunogenicity of replicase-based DNA vaccines. In vitro, cells transfected with replicase-based plasmids produce significantly more Type I IFNs than cells transfected with a conventional DNA plasmid. In vivo, replicase-based DNA vaccines yield stronger humoral responses in the absence of Type I IFN signaling but the lack of this signaling pathway in IFN-alphabeta receptor-/- (knockout) mice abolishes T cell mediated efficacy against tumors of both conventional and alphavirus replicase-based DNA vaccines. Moreover, the co-delivery of an IFNalpha-encoding plasmid significantly improved the efficacy of a weakly immunogenic conventional plasmid. These results suggest a central role for Type I IFNs in the mechanism of replicase-based DNA vaccines and indicate that vaccines can be enhanced by enabling their capacity to triggering innate anti-viral defense pathways.

Indexed as

RepliconAlphavirusAnimalsImmunizationInterferon Type IMelanoma, ExperimentalMembrane GlycoproteinsMiceMice, Inbred C57BLOxidoreductasesPlasmidsVaccines, DNAInterferon Type IMembrane GlycoproteinsOxidoreductasesTyrp1 protein, mouseVaccines, DNA

Identifiers

PMID16725231
PMCPMC1484849
OpenAlexW2037920701

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.