Evidence map›Paper›PMID 31551511›Full record

ArticleScientific reports2019

Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B meningococcal vaccine, 4CMenB, to the membrane-bound endotoxin of its outer membrane vesicle component.

Dylan Sheerin, Daniel O'Connor, Christina Dold, Elizabeth Clutterbuck, Moustafa Attar, Christine S Rollier, Manish Sadarangani, Andrew J Pollard

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Trial
  2. Article
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  4. Review
  5. Article
  6. Review
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 3 institutions in 2 countries.

Dylan SheerinOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK. dylan.sheerin@paediatrics.ox.ac.uk.
Daniel O'ConnorOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK.ORCID http://orcid.org/0000-0002-6902-9886
Christina DoldOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK.
Elizabeth ClutterbuckOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK.
Moustafa AttarWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Christine S RollierOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK.
Manish SadaranganiVaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
Andrew J PollardOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK.
Churchill Hospital · GBCentre for Human Genetics · GBUniversity of British Columbia · CA

Funding

Department of HealthMedical Research Council MR/M007693/1
6 · The paper itself

Abstract

The capsular group B meningococcal (MenB) four component vaccine (4CMenB) has been licensed for the prevention of invasive disease caused by MenB. The vaccine causes fever in infants, particularly when given in combination (concomitant) with other routinely-administered vaccines (routine), such as the standard diphtheria, tetanus, pertussis (DTP)-containing vaccine. To assess the suitability of a mouse immunisation model to study this phenomenon, we monitored temperature in mice after a second dose of routine vaccines, with or without 4CMenB, and compared the results with those in humans. Using this mouse model, we explored the reactogenicity of 4CMenB components by measuring changes in temperature, cytokines, and gene expression induced by 4CMenB, one of its components, wild-type or attenuated endotoxin outer membrane vesicles (OMVs), or lipopolysaccharide (LPS). A significant rise (p < 0.01) in temperature was observed in mice immunised with 4CMenB, wild-type OMVs, and LPS. RNA-sequencing of mouse whole blood revealed a gene signature shared by the 4CMenB, OMV, and LPS groups consisting of bacterial pattern recognition receptors and neutrophil activation marker genes. Sequencing of neutrophils isolated after concomitant 4CMenB identified cells expressing the OMV-associated genes Plek and Lcp1. Immunisation with 4CMenB or OMVs led to increased IL-6 in serum and significant upregulation (p < 0.0001) of prostaglandin-synthesising enzymes on brain tissue. These data demonstrate the suitability of a mouse model for assessing vaccine reactogenicity and strongly indicate that the fever following vaccination with 4CMenB in human infants is induced by endotoxin contained in the OMV component of the vaccine.

Indexed as

AnimalsAntibodies, BacterialBacterial Outer MembraneEndotoxinsFemaleImmunizationImmunization ScheduleInterleukin-6LipopolysaccharidesMeningococcal InfectionsMeningococcal VaccinesMiceMice, Inbred C57BLNeutrophilsSerum Bactericidal Antibody AssayTranscriptomeAntibodies, BacterialEndotoxinsInterleukin-6LipopolysaccharidesMeningococcal Vaccines

Identifiers

PMID31551511
PMCPMC6760121
OpenAlexW2976597620

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.