Evidence map›Paper›PMID 25953029›Full record

ArticleImmunology and cell biology2015

Modulating APOBEC expression enhances DNA vaccine immunogenicity.

Rafael Ribeiro Almeida, Rui André Saraiva Raposo, Fernanda Caroline Coirada, Jamile Ramos da Silva, Luís Carlos de Souza Ferreira, Jorge Kalil, Douglas F Nixon, Edecio Cunha-Neto

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In one paragraph

Article in Immunology and cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

5 citing papers in PubMed, 9 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

8 authors at 2 institutions in 2 countries.

Rafael Ribeiro AlmeidaDepartment of Medicine, Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Rui André Saraiva RaposoDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Fernanda Caroline CoiradaDepartment of Medicine, Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Jamile Ramos da SilvaDepartment of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Luís Carlos de Souza FerreiraDepartment of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Jorge KalilDepartment of Medicine, Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Douglas F NixonDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Edecio Cunha-NetoDepartment of Medicine, Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Universidade de São Paulo · BRGeorge Washington University · US

Funding

A novel APOBEC-based vaccine approach for HIVR33AI093179 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI NIXON, DOUGLAS F · 2014 to 2015
$1.5M
A novel APOBEC-based vaccine approach for HIVR21AI093179 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NIXON, DOUGLAS F · 2011 to 2012
$456k
NIAID NIH HHS AI093179
6 · The paper itself

Abstract

DNA vaccines have failed to induce satisfactory immune responses in humans. Several mechanisms of double-stranded DNA (dsDNA) sensing have been described, and modulate DNA vaccine immunogenicity at many levels. We hypothesized that the immunogenicity of DNA vaccines in humans is suppressed by APOBEC (apolipoprotein B (APOB) mRNA-editing, catalytic polypeptide)-mediated plasmid degradation. We showed that plasmid sensing via STING (stimulator of interferon (IFN) genes) and TBK-1 (TANK-binding kinase 1) leads to IFN-β induction, which results in APOBEC3A mRNA upregulation through a mechanism involving protein kinase C signaling. We also showed that murine APOBEC2 expression in HEK293T cells led to a 10-fold reduction in intracellular plasmid levels and plasmid-encoded mRNA, and a 2.6-fold reduction in GFP-expressing cells. A bicistronic DNA vaccine expressing an immunogen and an APOBEC2-specific shRNA efficiently silenced APOBEC2 both in vitro and in vivo, increasing the frequency of induced IFN-γ-secreting T cells. Our study brings new insights into the intracellular machinery involved in dsDNA sensing and how to modulate it to improve DNA vaccine immunogenicity in humans.

Indexed as

AnimalsAntigens, ViralAPOBEC DeaminasesApolipoproteins BCytidine DeaminaseHEK293 CellsHIV-1HLA-DR AntigensHumansImmunomodulationInterferon-betaMembrane ProteinsMiceMice, Inbred BALB CMice, KnockoutMice, TransgenicAntigens, ViralApobec2 protein, mouseAPOBEC3A protein, humanAPOBEC DeaminasesApolipoproteins BCytidine DeaminaseHLA-DR AntigensInterferon-betaMembrane ProteinsMuscle ProteinsPeptide FragmentsProteinsProtein Serine-Threonine KinasesRNA, Small InterferingSTING1 protein, humanSTING ProteinTBK1 protein, humanVaccines, DNA

Identifiers

PMID25953029
OpenAlexW261417378

What OpenQuestion holds

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Registered trials

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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.