Abstract
BackgroundPneumococcal infections are a major cause of morbidity and mortality in young children and immaturity of the immune system partly underlies poor vaccine responses seen in the young. Emerging evidence suggests a key role for epigenetics in the maturation and regulation of the immune system in health and disease. The study aimed to investigate epigenetic changes in early life and to understand the relationship between the epigenome and antigen-specific antibody responses to pneumococcal vaccination.MethodsThe epigenetic profiles from 24 healthy children were analyzed at 12 months prior to a booster dose of the 13-valent pneumococcal conjugate vaccine (PCV-13), and at 24 months of age, using the Illumina Methylation 450 K assay and assessed for differences over time and between high and low vaccine responders.ResultsOur analysis revealed 721 significantly differentially methylated positions between 12 and 24 months (FDR < 0.01), with significant enrichment in pathways involved in the regulation of cell–cell adhesion and T cell activation. Comparing high and low vaccine responders, we identified differentially methylated CpG sites (P value < 0.01) associated with HLA-DPB1 and IL6.ConclusionThese data imply that epigenetic changes that occur during early childhood may be associated with antigen-specific antibody responses to pneumococcal vaccines.
Highlights
Pneumococcal infections are a major cause of morbidity and mortality in young children and immatu‐ rity of the immune system partly underlies poor vaccine responses seen in the young
Young children are at higher risk of developing lifethreatening diseases compared with adults, which is thought to be due to the immaturity of their immune system
Twenty-four children (Table 1) who had received the 13-valent pneumococcal conjugate vaccine (PCV-13) at 12 months of age, as part of a previously published clinical trial [19,20,21], were selected based on their aggregated Immunoglobulin G (IgG) antibody response and categorized into high and low responders (Fig. 1 and Additional file 1: Figure 1). This categorization was valid for post-booster serotype-specific opsonophagocytic assay (OPA) titers and memory B cells responses (Additional file 1: Figures 2 and 3), truly grouping individuals into high and low vaccine responders
Summary
Pneumococcal infections are a major cause of morbidity and mortality in young children and immatu‐ rity of the immune system partly underlies poor vaccine responses seen in the young. Young children are at higher risk of developing lifethreatening diseases compared with adults, which is thought to be due to the immaturity of their immune system. They show reduced immune responses to vaccines [1]. Pneumococcal infections are a major public health problem worldwide causing high morbidity and mortality in young children who suffer pneumonia, meningitis and septicemia, leading up to 1 million deaths in children under the age of five years [2, 3]. There is great variability in the immune response to vaccination in children, with some individuals achieving more than 100-fold higher antibody levels post-immunization than others [5, 6]. The reason for this huge variation is not understood, and recent studies have begun to reveal the genetic determinants of immune responses to vaccines [7, 8]
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