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

Molecular Systems Biology
Daniel O'ConnorAndrew J Pollard

Abstract

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...Continue Reading

Associated Clinical Trials

References

Feb 1, 1990·The Biochemical Journal·P C HeinrichT Andus
Jun 1, 1969·The Journal of Experimental Medicine·I GoldschneiderM S Artenstein
Feb 19, 2000·Biochemical and Biophysical Research Communications·M K SongI H Choi
Mar 5, 2003·International Journal of Antimicrobial Agents·Annelies Wilder-Smith, Ziad Memish
Dec 16, 2006·Science·Yu ChenWolfgang G Junger
Jan 9, 2007·Nature Genetics·Richard S SpielmanVivian G Cheung
Jul 3, 2007·Lancet·David S StephensPetter Brandtzaeg
Dec 15, 2007·The American Journal of Pathology·Alexander Zarbock, Klaus Ley
Sep 19, 2008·Nature Immunology·Tracy S P HengUNKNOWN Immunological Genome Project Consortium
Mar 4, 2010·Genome Biology·Mark D Robinson, Alicia Oshlack
Jul 26, 2011·Nature Reviews. Immunology·Alberto MantovaniSébastien Jaillon
Oct 14, 2011·Methods in Molecular Biology·Nadine G Rouphael, David S Stephens
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Mar 14, 2013·Critical Reviews in Clinical Laboratory Sciences·James D Faix
Sep 26, 2013·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Matthew D SnapeAndrew J Pollard
Dec 18, 2013·Immunity·Cecilia GarlandaAlberto Mantovani
Feb 4, 2014·Genome Biology·Charity W LawGordon K Smyth
May 3, 2014·The New England Journal of Medicine·Suzanne T AndersonBrian Eley
Aug 19, 2014·Cytokine & Growth Factor Reviews·Linda J Bendall, Kenneth F Bradstock
Nov 5, 2014·Expert Opinion on Therapeutic Patents·Christopher J PelhamDevendra K Agrawal
Nov 27, 2014·Human Vaccines & Immunotherapeutics·Roman PrymulaPeter M Dull
Nov 27, 2014·Human Vaccines & Immunotherapeutics·Susanna EspositoDaniela Toneatto
Dec 9, 2014·Expert Opinion on Biological Therapy·Christine S RollierAndrew J Pollard
Jan 18, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine B ReadVibeke W Stennicke
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Mar 31, 2015·Nature Methods·Aaron M NewmanAsh A Alizadeh

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE131929

Methods Mentioned

BETA
PCA
genetic modification
MDS

Clinical Trials Mentioned

NCT02080559

Software Mentioned

sdwd
ImmQuant
limma
HISAT2
R package “ caret
voom
tmod ” R package
xPonent
HTSeq
R Bioconductor

Related Concepts