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

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.

Differentiating vaccine reactions from invasive bacterial infections in young infants presenting to the emergency department in the 4CMenB era: a retrospective observational comparison

“…Our results clearly demonstrate a rise in inflammatory markers post vaccination, as has previously been reported post immunisation even in children not requiring medical attention. 8 We observed that neither WCC or neutrophils are helpful in predicting IBI in this context. This is consistent with known limitations in their use outside the post immunisation period.…”

“…2 Additionally, the immunological response to vaccination is known to cause a transient rise in inflammatory markers in infants with and without AEFI. In particular CRP, granulocyte colony stimulating factor, interleukin (IL)-1RA and IL-6 have been shown to rise 24 hours post vaccination, with corresponding neutrophil activation, 8 further complicating differentiating AEFI from IBI.…”

“…To better inform the potential role of routine inflammatory markers in assessing children on presentation to ED post vaccination, we included blood results from a third group of children, recruited into the European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) into the immunogenicity of the 4CMenB vaccination. 8 In this study, all patients received routine immunisations at 4 months of age according to the UK 2015 immunisation schedule (online supplemental table 1), with half also receiving 4CMenB vaccination. Blood Open access samples were taken from these infants at one of four timepoints post vaccination (either 4, 24 and 72 hours or 7 days), regardless of whether or not they exhibited any symptoms or signs of clinical illness.…”

Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children

“…Systems biology approaches have been used to evaluate immune responses to vaccines, e.g. yellow fever (15)(16)(17), meningococcus (18,19), pneumococcal (18,20) and influenza (21)(22)(23) and have been powerful tools for elucidating immunological correlates of vaccine responses. In the context of seasonal influenza vaccination, gene sets related to immunoglobulins, complement proteins, and cellular proliferation are strongly enriched in vaccine responders compared to non-responders 7 days post-vaccination (22).…”

Distinct patterns of whole blood transcriptional responses are induced in mice following immunisation with adenoviral and poxviral vector vaccines encoding the same antigen

“…This approach has also been extended into mice for the exploratory analysis of different vaccine platforms and components through whole blood transcriptomics, for example for the acellular pertussis vaccine and pertussis outer membrane vesicles (OMVs) [ 25 , 26 ], and a variety of novel vaccine adjuvants [ 27 ]. We previously applied comparative transcriptomics to identify molecular determinants of vaccine-induced reactogenicity within the first 24 h post-immunisation in mice and infants [ 28 , 29 ]. There is a paucity of data related to the transcriptional responses induced by viral vector vaccines.…”