Evidence map›Paper›PMID 24325826›Full record

ArticleVaccine2014

Type I interferon-dependent activation of NK cells by rAd28 or rAd35, but not rAd5, leads to loss of vector-insert expression.

Matthew J Johnson, Niklas K Björkström, Constantinos Petrovas, Frank Liang, Jason G D Gall, Karin Loré, Richard A Koup

Abstract read
In one paragraph

Article in Vaccine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
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  7. Article
  8. Article
  9. Article
  10. Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  11. Review
  12. Article
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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

7 authors at 3 institutions in 2 countries.

Matthew J JohnsonImmunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20007, USA.
Niklas K BjörkströmPathology Department, Center for Infectious Medicine, Karolinska Institutet, Stockholm 14186, Sweden; Department of Medicine, Karolinska Institutet, Stockholm 14186, Sweden.
Constantinos PetrovasImmunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Frank LiangImmunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Pathology Department, Center for Infectious Medicine, Karolinska Institutet, Stockholm 14186, Sweden; Department of Medicine, Karolinska Institutet, Stockholm 14186, Sweden.
Jason G D GallGenVec, Inc., Gaithersburg, MD 20878, USA.
Karin LoréImmunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Pathology Department, Center for Infectious Medicine, Karolinska Institutet, Stockholm 14186, Sweden; Department of Medicine, Karolinska Institutet, Stockholm 14186, Sweden.
Richard A KoupImmunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rkoup@mail.nih.gov.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USGenVec · US

Funding

Testing of Blood Samples for Immune Response and Vaccine ResearchZIAAI005073 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KOUP, RICHARD A · 2009 to 2025
$23.4M
Intramural NIH HHS ZIA AI005073
6 · The paper itself

Abstract

Vaccines constructed from rare-serotype recombinant adenovirus vectors (rAd) such as rAd serotype 28 (rAd28) and rAd35 are currently being explored as alternatives to rAd5-based vaccines because they circumvent the problems with pre-existing immunity that complicate the effectiveness of rAd5 vaccines. However, previous work has demonstrated that the immunogenicity of rAd28 and rAd35 is substantially lower than rAd5. Here we show that rAd28 and rAd35 increase apoptosis of antigen presenting cells (APCs), such as monocytes, relative to rAd5 and mock infected controls. APCs undergoing apoptosis showed an increased loss of vector-insert expression. Loss of vector-insert expression correlated with activation of NK cells, which resulted in apoptosis of co-cultured monocytes. Finally, we show that activation of NK cells is dependent on IFNα which is produced by exposure to rAd28 or rAd35, but not to rAd5. Taken together, these data demonstrate that IFNα-induced activation of NK cells leads to increased monocyte apoptosis and subsequent vector-insert loss. This may be a possible mechanism that results in reduced immunogenicity of rAd28 and rAd35-based vectors.

Indexed as

AdenoviridaeLymphocyte ActivationApoptosisCells, CulturedGenetic VectorsHumansInterferon-alphaKiller Cells, NaturalLipopolysaccharide ReceptorsMonocytesInterferon-alphaLipopolysaccharide ReceptorsAdenovirusrAd28rAd35

Identifiers

PMID24325826
PMCPMC3946768
OpenAlexW1967004905

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.