Background

In 2015, 4CMenB (Bexsero®) was added to the UK infant vaccination schedule to protect infants against invasive meningococcal disease with capsular group B meningococcus. 4CMenB is efficacious but reactogenic, and has led to an increase in infant hospital admissions for infection screens due to vaccine related fever. This study investigated the innate immune response to vaccination in infants and its relationship to the increased reactogenicity of the current 4CMenB containing schedule.

Methods

4-month-old infants were randomised to receive pre-2015 vaccinations alone or alongside 4CMenB (current schedule). Plasma protein expression was profiled using mass spectrometry (LC-MS/MS) and Luminex® multiplex bead-based immunoassays to measure high and low abundance proteins respectively. Plasma from thirty infants was profiled at baseline and 4-hours (n=13) or 24-hours (n=17) post vaccination. Foldchanges were determined using paired Wilcox-tests (Luminex data) and linear models (mass-spectrometry data). Results with FDR<0.05 were deemed significant.

Results

Compared with baseline samples, 4 and 29 proteins were differentially expressed at 4-hours and 24-hours after vaccination respectively. Eight proteins correlated with neutrophil counts and/or post-vaccine temperature. Differentially expressed proteins were enriched in 30 REACTOME pathways; enriched terms included neutrophil degranulation, haemostasis, retinoid metabolism and lipid metabolism.

Seven proteins were more highly expressed at 4-hours (Apolipoprotein-A1, Apolipoprotein-A2, and Apolipoprotein-C1) and 24-hours (CRP, serum amyloid-A2, G-CSF and IL-6) post vaccination in the 4CMenB group, potentially reflecting the increased reactogenicity of the current vaccine schedule.

Proteomic and transcriptomic data were integrated to create networks summarising the innate immune response to vaccination.

Conclusions

This is the first study investigating the effect of vaccination on the plasma proteome. These findings provide new insights into the immune response to vaccination and vaccine reactogenicity, potentially informing the design of less reactogenic vaccines and vaccine schedules.

Clinical Trial Registration

EudraCT number 2014-000126-38