Sara Pischedda1,2,3, Daniel O'Connor4, Benjamin P Fairfax5, Antonio Salas6,7, Federico Martinon-Torres6,8, Andrew J Pollard9, Johannes Trück10,11. 1. Genetics, Vaccines and Infections and Pediatrics Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain. sara.pischedda01@gmail.com. 2. Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. sara.pischedda01@gmail.com. 3. Hospital Clínico Universitario de Santiago (SERGAS), Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Galicia, Spain. sara.pischedda01@gmail.com. 4. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and The NIHR Oxford Biomedical Research Centre, Oxford, UK. daniel.oconnor@paediatrics.ox.ac.uk. 5. MRC-Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. 6. Genetics, Vaccines and Infections and Pediatrics Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain. 7. Hospital Clínico Universitario de Santiago (SERGAS), Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Galicia, Spain. 8. Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 9. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and The NIHR Oxford Biomedical Research Centre, Oxford, UK. 10. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and The NIHR Oxford Biomedical Research Centre, Oxford, UK. johannes.trueck@kispi.uzh.ch. 11. Division of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich (UZH), Zurich, Switzerland. johannes.trueck@kispi.uzh.ch.
Abstract
BACKGROUND: Pneumococcal 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. METHODS: The 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. RESULTS: Our 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. CONCLUSION: These data imply that epigenetic changes that occur during early childhood may be associated with antigen-specific antibody responses to pneumococcal vaccines.
BACKGROUND: Pneumococcal 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. METHODS: The 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. RESULTS: Our 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. CONCLUSION: These data imply that epigenetic changes that occur during early childhood may be associated with antigen-specific antibody responses to pneumococcal vaccines.
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