Evidence map›Paper›PMID 29415180›Full record

Trial reportThe Journal of infectious diseases2018

Neonatal BCG Vaccination Influences Cytokine Responses to Toll-like Receptor Ligands and Heterologous Antigens.

Bridget Freyne, Susan Donath, Susan Germano, Kaya Gardiner, Dan Casalaz, Roy M Robins-Browne, Nelly Amenyogbe, Nicole L Messina, Mihai G Netea, Katie L Flanagan and 2 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05168709 (A Single-arm Clinical Trial to Investigate COVID-19 Specific Vaccine and Heterologous Immunity in the Melbourne Infant Study of BCG for Allergy and Infection Reduction), which is not on this map. Cited by 51 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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.

NCT05168709 phase4completednot on this mapstarted 2022, after this paper: background citation

A Single-arm Clinical Trial to Investigate COVID-19 Specific Vaccine and Heterologous Immunity in the Melbourne Infant Study of BCG for Allergy and Infection Reduction (COSI BAIR)

TypeinterventionalSponsorMurdoch Childrens Research InstituteRan2022 to 2022Enrolled51ConditionsCOVID-19, Vaccine Reaction, Immunization, InfectionArmsTozinameran
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
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  13. Innate immune training in the neonatal response to sepsis.Molecular medicine (Cambridge, Mass.) · 2025
    Article
  14. Recent Advances of Trained immunity in Macrophages.International journal of biological sciences · 2025
    Review
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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

12 authors at 8 institutions in 3 countries.

Bridget FreyneInfectious Diseases and Microbiology Group, Parkville, Australia.
Susan DonathClinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Australia.
Susan GermanoInfectious Diseases and Microbiology Group, Parkville, Australia.
Kaya GardinerInfectious Diseases and Microbiology Group, Parkville, Australia.
Dan CasalazDepartment of Paediatrics, Mercy Hospital for Women, Heidelberg, Australia.
Roy M Robins-BrowneInfectious Diseases and Microbiology Group, Parkville, Australia.
Nelly AmenyogbeDepartment of Experimental Medicine, University of British Columbia, Vancouver, Canada.
Nicole L MessinaInfectious Diseases and Microbiology Group, Parkville, Australia.
Mihai G NeteaDepartment of Internal Medicine, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Katie L FlanaganSchool of Medicine, University of Tasmania, Launceston Australia.
Tobias KollmannDepartment of Experimental Medicine, University of British Columbia, Vancouver, Canada.
Nigel CurtisInfectious Diseases and Microbiology Group, Parkville, Australia.
Parks Victoria · AUUniversity of British Columbia · CAMercy Hospital for Women · AUMurdoch Children's Research Institute · AURadboud Institute for Molecular Life Sciences · NLRoyal Children's Hospital · AUThe University of Melbourne · AUUniversity of Tasmania · AU

Funding

Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2017 to 2021
$24.7M
European Research Council 310372NIAID NIH HHS U19 AI118608
6 · The paper itself

Abstract

Background: BCG vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The underlying mechanisms remain uncertain, but long-term modulation of the innate immune response (trained immunity) may be involved. Methods: Whole-blood specimens, collected 7 days after randomization from 212 neonates enrolled in a randomized trial of neonatal BCG vaccination, were stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses. Results: BCG-vaccinated infants had increased production of interleukin 6 (IL-6) in unstimulated samples and decreased production of interleukin 1 receptor antagonist, IL-6, and IL-10 and the chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and monocyte chemoattractant protein 1 (MCP-1) following stimulation with peptidoglycan (TLR2) and R848 (TLR7/8). BCG-vaccinated infants also had decreased MCP-1 responses following stimulation with heterologous pathogens. Sex and maternal BCG vaccination status interacted with neonatal BCG vaccination. Conclusions: Neonatal BCG vaccination influences cytokine responses to TLR ligands and heterologous pathogens. This effect is characterized by decreased antiinflammatory cytokine and chemokine responses in the context of higher levels of IL-6 in unstimulated samples. This supports the hypothesis that BCG vaccination modulates the innate immune system. Further research is warranted to determine whether there is an association between these findings and the beneficial nonspecific (heterologous) effects of BCG vaccine on all-cause mortality.

Indexed as

AdultAntigens, HeterophileBCG VaccineChemokine CCL2Chemokine CCL3Chemokine CCL4CytokinesFemaleHumansInterleukin-10Interleukin-6LigandsMaleToll-Like Receptor 2Toll-Like ReceptorsVaccinationAntigens, HeterophileBCG VaccineChemokine CCL2Chemokine CCL3Chemokine CCL4CytokinesInterleukin-10Interleukin-6LigandsToll-Like Receptor 2Toll-Like Receptors

Identifiers

PMID29415180
PMCPMC11491830
OpenAlexW2793717126

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.