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

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

doi:10.15252/msb.20209888

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.

Highlights

Neisseria meningitidis is a major cause of meningitis and septicaemia
Principal component (PC) analysis of CIBERSORT cell fraction data showed clustering of early post-vaccination samples, and the most important contributor to this clustering (PC1) was the neutrophil count (Appendix Fig S3). These analyses reveal that an increase in neutrophils early post-vaccination is associated with comprehensive changes to the underlying structure to the blood transcriptome (Fig 2B)
We explored the ability of baseline transcriptomic data to predict subsequent vaccine-induced immunity

Summary

Introduction

Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. 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. Blood gene expression and plasma proteins were measured prior to, 4 h, 24 h, 3 days or 7 days post-vaccination. 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. We present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine

Objectives

Methods

Findings

Conclusion