Evidence map›Paper›PMID 21427227›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection.

Kerry A Millington, Sarah M Fortune, Jeffrey Low, Alejandra Garces, Suzanne M Hingley-Wilson, Melissa Wickremasinghe, Onn M Kon, Ajit Lalvani

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 140 citations in OpenAlex.

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  7. Assembly of theMicrobiology spectrum · 2025
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  10. Role of MHC class I pathways inFrontiers in cellular and infection microbiology · 2023
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  11. Evaluation of the Immunogenicity of Recombinant Espb, Espc Proteins fromReports of biochemistry & molecular biology · 2023
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  14. A fluorescence polarization assay using recombinant proteinIranian journal of veterinary research · 2022
    Article
  15. Article
  16. An Immunoinformatic Strategy to Develop NewInternational journal of peptide research and therapeutics · 2022
    Article
  17. Article
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  19. Pan and Core Genome Analysis of 183Antibiotics (Basel, Switzerland) · 2021
    Article
  20. Article

18 more citing papers are in PubMed but not listed here.

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 5 institutions in 2 countries.

Kerry A MillingtonTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London W2 1PG, United Kingdom.
Sarah M Fortune
Jeffrey Low
Alejandra Garces
Suzanne M Hingley-Wilson
Melissa Wickremasinghe
Onn M Kon
Ajit Lalvani
Harvard University · USImperial College London · GBSt. Mary's Hospital · GBNational Health Service · GBSt Mary's Hospital · GB

Funding

PE and PPE FunctionR21AI070871 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI FORTUNE, SARAH · 2007 to 2008
$430k
NIAID NIH HHS 5R21AI70871NIAID NIH HHS R21 AI070871Wellcome Trust
6 · The paper itself

Abstract

The 6-kDa early secretory antigenic target of Mycobacterium tuberculosis (ESAT-6) and the 10-kDa culture filtrate antigen (CFP-10), encoded in region of difference 1 (RD1) and secreted by the ESAT-6 system 1 (Esx-1) secretion system, are the most immunodominant and highly M. tuberculosis (MTB)-specific antigens. These attributes are responsible for their primary importance in tuberculosis (TB) immunodiagnosis and vaccine development. Rv3615c [Esx-1 substrate protein C (EspC)], encoded outside RD1, is similar in size and sequence homology to CFP-10 and ESAT-6, suggesting it might be a target of cellular immunity in TB. Using ex vivo enzyme-linked immunospot- and flow cytometry-based cytokine-secretion assay, we comprehensively assessed cellular immune responses to EspC in patients with active TB, latently infected persons, and uninfected bacillus Calmette-Guérin (BCG)-vaccinated controls. EspC was at least as immunodominant as ESAT-6 and CFP-10 in both active and latent TB infection. EspC contained broadly recognized CD4(+) and CD8(+) epitopes, inducing a predominantly CD4(+) T-cell response that comprised functional T-cell subsets secreting both IFN-γ and IL-2 as well as functional T-cell subsets secreting only IFN-γ. Surprisingly, T-cell responses to EspC were as highly specific (93%) for MTB infection as responses to ESAT-6 and CFP-10, with only 2 of 27 BCG-vaccinated controls responding to each antigen. Using quantitative proteomics and metabolically labeled mutant and genetically complemented MTB strains, we identified the mechanism of the specificity of anti-EspC immunity as the Esx-1 dependence of EspC secretion. The high immunodominance of EspC, equivalent to that of ESAT-6 and CFP-10, makes it a TB vaccine candidate, and its high specificity confers strong potential for T-cell-based immunodiagnosis.

Indexed as

Antigens, BacterialBacterial ProteinsBCG VaccineEnzyme-Linked Immunospot AssayFlow CytometryHumansImmunodominant EpitopesMycobacterium tuberculosisProteomicsT-Lymphocyte SubsetsTuberculosisAntigens, BacterialBacterial ProteinsBCG VaccineCFP-10 protein, Mycobacterium tuberculosisESAT-6 protein, Mycobacterium tuberculosisImmunodominant Epitopes

Identifiers

PMID21427227
PMCPMC3078386
OpenAlexW2023774776

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.