Evidence map›Paper›PMID 27519524›Full record

ArticleBMC infectious diseases2016

A new tool for tuberculosis vaccine screening: Ex vivo Mycobacterial Growth Inhibition Assay indicates BCG-mediated protection in a murine model of tuberculosis.

Andrea Zelmer, Rachel Tanner, Elena Stylianou, Timon Damelang, Sheldon Morris, Angelo Izzo, Ann Williams, Sally Sharpe, Ilaria Pepponi, Barry Walker and 4 more

Open access · goldAbstract read
In one paragraph

Article in BMC infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  5. Recombinant BCG vaccine expressing multistage antigens ofHuman vaccines & immunotherapeutics · 2024
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  9. TheF1000Research · 2021
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  12. Observational
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  16. Article
  17. Frontiers in immunology · 2018
    Article
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  19. 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

14 authors at 7 institutions in 3 countries.

Andrea ZelmerLondon School of Hygiene and Tropical Medicine, London, UK. andrea.zelmer@lshtm.ac.uk.ORCID 0000-0001-9621-4406
Rachel TannerThe Jenner Institute, Oxford University, Oxford, UK.
Elena StylianouThe Jenner Institute, Oxford University, Oxford, UK.
Timon DamelangLondon School of Hygiene and Tropical Medicine, London, UK.
Sheldon MorrisCenter for Biologics Evaluation and Research, Silver Spring, MD, USA.
Angelo IzzoColorado State University, Fort Collins, CO, USA.
Ann WilliamsPublic Health England, Porton Down, UK.
Sally SharpePublic Health England, Porton Down, UK.
Ilaria PepponiThe Jenner Institute, Oxford University, Oxford, UK.
Barry WalkerAeras, Rockville, MD, USA.
David A HokeyAeras, Rockville, MD, USA.
Helen McShaneThe Jenner Institute, Oxford University, Oxford, UK.
Michael BrennanAeras, Rockville, MD, USA.
Helen FletcherLondon School of Hygiene and Tropical Medicine, London, UK.
Aeras · USLondon School of Hygiene & Tropical Medicine · GBUniversity of Oxford · GBPublic Health England · GBAnimal and Plant Health Agency · GBCenter for Biologics Evaluation and Research · USColorado State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn the absence of a validated animal model and/or an immune correlate which predict vaccine-mediated protection, large-scale clinical trials are currently the only option to prove efficacy of new tuberculosis candidate vaccines. Tools to facilitate testing of new tuberculosis (TB) vaccines are therefore urgently needed.

methodsWe present here an optimized ex vivo mycobacterial growth inhibition assay (MGIA) using a murine Mycobacterium tuberculosis infection model. This assay assesses the combined ability of host immune cells to inhibit mycobacterial growth in response to vaccination. C57BL/6 mice were immunized with Bacillus Calmette-Guérin (BCG) and growth inhibition of mycobacteria by splenocytes was assessed. Mice were also challenged with Mycobacterium tuberculosis Erdman, and bacterial burden was assessed in lungs and spleen.

resultsUsing the growth inhibition assay, we find a reduction in BCG CFU of 0.3-0.8 log10 after co-culture with murine splenocytes from BCG vaccinated versus naïve C57BL/6 mice. BCG vaccination in our hands led to a reduction in bacterial burden after challenge with Mycobacterium tuberculosis of approx. 0.7 log10 CFU in lung and approx. 1 log10 CFU in spleen. This effect was also seen when using Mycobacterium smegmatis as the target of growth inhibition. An increase in mycobacterial numbers was found when splenocytes from interferon gamma-deficient mice were used, compared to wild type controls, indicating that immune mechanisms may also be investigated using this assay.

conclusionsWe believe that the ex vivo mycobacterial growth inhibition assay could be a useful tool to help assess vaccine efficacy in future, alongside other established methods. It could also be a valuable tool for determination of underlying immune mechanisms.

Indexed as

AnimalsBCG VaccineCoculture TechniquesColony Count, MicrobialDisease Models, AnimalDrug Evaluation, PreclinicalFemaleInterferon-gammaMiceMice, Inbred C57BLMice, Mutant StrainsMycobacterium bovisMycobacterium smegmatisMycobacterium tuberculosisSpleenTuberculosisBCG VaccineInterferon-gammaTuberculosis VaccinesGrowth inhibition assayMycobacteriaTuberculosisVaccines

Identifiers

PMID27519524
PMCPMC4983071
OpenAlexW2512385601

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.