ArticlePloS one2013
Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- MVA85A vaccine to enhance BCG for preventing tuberculosis.The Cochrane database of systematic reviews · 2019Pooled it
- A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection.Frontiers in immunology · 2018Trial
- Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects.Journal of the International AIDS Society · 2017Trial
- Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response.BMC infectious diseases · 2014Trial
- Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγtGut microbes · 2023Article
- Combination of Taurine and Black Pepper Extract as a Treatment for Cardiovascular and Coronary Artery Diseases.Nutrients · 2023Review
- TIRAP, TRAM, and Toll-Like Receptors: The Untold Story.Mediators of inflammation · 2023Review
- The Immune Signatures data resource, a compendium of systems vaccinology datasets.Scientific data · 2022Article
- A Review of Human Coronaviruses' Receptors: The Host-Cell Targets for the Crown Bearing Viruses.Molecules (Basel, Switzerland) · 2021Review
- Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion.Biomedicines · 2021Review
- Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?International journal of molecular sciences · 2021Review
- Differential DNA methylation of potassium channel KCa3.1 and immune signalling pathways is associated with infant immune responses following BCG vaccination.Scientific reports · 2018Article
- Novel polymorphisms inGlobal health, epidemiology and genomics · 2018Article
- Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or Regulatory T Cell Responses in Adults.Clinical and vaccine immunology : CVI · 2015Article
- Recent advances in the development of vaccines for tuberculosis.Therapeutic advances in vaccines · 2015Review
- Polymorphisms in TICAM2 and IL1B are associated with TB.Genes and immunity · 2015Article
- Regulatory T-Cells at the Interface between Human Host and Pathogens in Infectious Diseases and Vaccination.Frontiers in immunology · 2015Review
- Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A.BMC infectious diseases · 2014Article
- IL-32 is a molecular marker of a host defense network in human tuberculosis.Science translational medicine · 2014Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.
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Registered trials
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.