Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine.


Journal

Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389

Informations de publication

Date de publication:
11 2020
Historique:
received: 26 07 2020
revised: 06 10 2020
accepted: 08 10 2020
entrez: 19 11 2020
pubmed: 20 11 2020
medline: 26 8 2021
Statut: ppublish

Résumé

Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post-vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP-IPV-Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post-vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G-CSF, IL-1RA and IL-6. Post-vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin-3, -5 and GM-CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine.

Identifiants

pubmed: 33210468
doi: 10.15252/msb.20209888
pmc: PMC7674973
doi:

Substances chimiques

13-valent pneumococcal vaccine 0
Diphtheria-Tetanus-Pertussis Vaccine 0
Haemophilus Vaccines 0
Meningococcal Vaccines 0
Pneumococcal Vaccines 0
Poliovirus Vaccine, Inactivated 0
Proteome 0
Vaccines, Conjugate 0
diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine 0

Banques de données

GEO
['GSE131929', 'GSE132199']
ClinicalTrials.gov
['NCT02080559']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

e9888

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M007693/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 090532/Z/09/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

© 2020 The Authors. Published under the terms of the CC BY 4.0 license.

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Auteurs

Daniel O'Connor (D)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Marta Valente Pinto (MV)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Dylan Sheerin (D)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Adriana Tomic (A)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.

Ruth E Drury (RE)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Samuel Channon-Wells (S)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Ushma Galal (U)

Nuffield Department of Primary Health Care, Clinical Trials Unit, University of Oxford, Oxford, UK.

Christina Dold (C)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Hannah Robinson (H)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Simon Kerridge (S)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Emma Plested (E)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Harri Hughes (H)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Lisa Stockdale (L)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Manish Sadarangani (M)

Department of Pediatrics, University of British Columbia, Vancouver, Canada.

Matthew D Snape (MD)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Christine S Rollier (CS)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Michael Levin (M)

Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.

Andrew J Pollard (AJ)

Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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