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

Mol Syst Biol. 2020 Nov;16(11):e9888. doi: 10.15252/msb.20209888.


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.

Trial registration: NCT02080559.

Keywords: paediatrics; proteomics; systems biology; transcriptomics; vaccines.

Publication types

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

MeSH terms

  • Animals
  • Blood Chemical Analysis
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology
  • Female
  • Fever / blood
  • Fever / epidemiology
  • Fever / etiology
  • Fever / genetics*
  • Gene Expression Profiling
  • Haemophilus Vaccines / adverse effects
  • Haemophilus Vaccines / immunology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity / genetics*
  • Incidence
  • Infant
  • Male
  • Meningococcal Infections / prevention & control
  • Meningococcal Vaccines / adverse effects
  • Meningococcal Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Pneumococcal Vaccines / adverse effects
  • Pneumococcal Vaccines / immunology
  • Poliovirus Vaccine, Inactivated / adverse effects
  • Poliovirus Vaccine, Inactivated / immunology
  • Proteome / analysis
  • Transcriptome
  • Vaccination / adverse effects
  • Vaccines, Conjugate / adverse effects
  • Vaccines, Conjugate / immunology


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

Associated data

  • GEO/GSE131929
  • GEO/GSE132199