Evidence map›Paper›PMID 38956057›Full record

ArticleNPJ vaccines2024

A modified mycobacterial growth inhibition assay for the functional assessment of vaccine-mediated immunity.

Emil Joseph Vergara, Andy Cano Tran, Matthew J Paul, Thomas Harrison, Andrea Cooper, Rajko Reljic

Abstract read
In one paragraph

Article in NPJ vaccines, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

6 authors.

Emil Joseph VergaraInstitute for Infection and Immunity, St. George's University of London, London, UK.ORCID http://orcid.org/0000-0002-4806-0083
Andy Cano TranInstitute for Infection and Immunity, St. George's University of London, London, UK.ORCID http://orcid.org/0000-0003-4019-1318
Matthew J PaulInstitute for Infection and Immunity, St. George's University of London, London, UK.
Thomas HarrisonInstitute for Infection and Immunity, St. George's University of London, London, UK.
Andrea CooperDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Rajko ReljicInstitute for Infection and Immunity, St. George's University of London, London, UK. rreljic@sgul.ac.uk.

Funding

European Commission (EC) 860325Medical Research Council MR/P011136/1
6 · The paper itself

Abstract

The Mycobacterial growth inhibition assay (MGIA) is an ex-vivo assay used to measure the overall functional immune response elicited by infection or vaccination. In tuberculosis (TB) vaccine development, MGIA is a potentially important tool for preclinical evaluation of early-stage vaccine candidates to complement existing assays, and to potentially reduce the need for lengthy and costly pathogenic Mycobacterium tuberculosis (Mtb) animal challenge experiments. The conventional method of MGIA in mice entails directly infecting mixed cell cultures, most commonly splenocytes, from immunised mice with mycobacteria. However, this direct infection of mixed cell populations may yield unreliable results and lacks sufficient sensitivity to discriminate well between different vaccines due to the low number of mycobacteria-permissive cells. Here, we modified the assay by inclusion of mycobacteria-infected congenic murine macrophage cell lines as the target cells, and by measuring the total number of killed cells rather than the relative reduction between different groups. Thus, using splenocytes from Mycobacterium bovis BCG immunised mice, and J774 and MH-S (BALB/c background) or BL/6-M (C57Bl/6 background) macrophage cell lines, we demonstrated that the modified assay resulted in at least 26-fold greater mycobacterial killing per set quantity of splenocytes as compared to the conventional method. This increased sensitivity of measuring mycobacterial killing was confirmed using both the standard culture forming unit (CFU) assay and luminescence readings of luciferase-tagged virulent and avirulent mycobacteria. We propose that the modified MGIA can be used as a highly calibrated tool for quantitating the killing capacity of immune cells in preclinical evaluation of vaccine candidates for TB.

Identifiers

PMID38956057
PMCPMC11219912

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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.