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

Daniel O’Connor, Marta Valente Pinto, Dylan Sheerin, Adriana Tomic, Ruth E. Drury, Samuel Channon-Wells, Ushma Galal, Christina Dold, Hannah Robinson, Simon Kerridge, Emma Plested, Harri Hughes, Lisa Stockdale, Manish Sadarangani, Matthew D. Snape, Christine S. Rollier, Michael Levin, Andrew J. Pollard

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 vaccine.

Original languageEnglish
Article numbere9888
JournalMolecular Systems Biology
Volume16
Issue number11
DOIs
Publication statusPublished - Nov 2020
Externally publishedYes

Keywords

  • paediatrics
  • proteomics
  • systems biology
  • transcriptomics
  • vaccines

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