title: Memory B cell response to a PCV-13 booster in 3.5year old children primed with either PCV-7 or PCV-13.
abstract: Pneumococcal protein-polysaccharide conjugate vaccines provide direct protection against Streptococcus pneumoniae through the induction of persistent anti-polysaccharide antibodies, and by priming for a rapid secondary antibody response. Memory B cells (BMEM) generated during an initial immune response are responsible for both the more rapid and quantitatively greater secondary antibody response and are also thought to contribute to the ongoing production of plasma cells providing long-term antibody persistence. We recruited 3.5-year-old children who had participated in a previous clinical trial comparing infant immunization with either a 7-valent (PCV-7) or a 13-valent pneumococcal conjugate vaccine (PCV-13) to investigate whether prior priming with pneumococcal antigens influences BMEMresponses. Blood was taken before and 1month after a PCV-13 booster. BMEMwere quantified using a cultured ELISpot assay for pneumococcal serotypes 1, 3, 4, 14, 19A, 23F, and with diphtheria and tetanus toxoid as controls, and then correlated with serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers. In total, blood samples from 62 participants were available for analysis. Serotype-specific BMEMfrequencies were generally low at baseline (before boost) although for serotypes 14 and 3, they were significantly higher in children primed with PCV-13 than PCV-7 primed children. Following the PCV-13 booster, BMEMfrequencies increased and were not different between the groups for all serotypes. A strong inverse correlation was found between antibody concentrations and OPA titers at baseline and BMEMfollowing booster vaccination for serotype 3 but not for other serotypes suggesting that, for this serotype, pre-existing serotype-specific antibodies may inhibit BMEMformation in response to vaccination. Clinicaltrials.gov registration number: NCT01095471.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: johannes.trueck@kispi.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Trück
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Amber
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Bristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.
authors.forename: Begonia
authors.initials: B
authors.lastname: Morales-Aza
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Clutterbuck
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Merryn
authors.initials: M
authors.lastname: Voysey
authors.affiliation: Bristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK; Vaccines and Immunity Theme, MRC Unit, The Gambia, Gambia.
authors.forename: Ed
authors.initials: E
authors.lastname: Clarke
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Snape
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Dominic F
authors.initials: DF
authors.lastname: Kelly
authors.affiliation: Bristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D008297:Male; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines
keywords: Antibodies; B cells; Children; Conjugate vaccine; Memory; Memory B cells; Persistence; Serotype 3; Streptococcus pneumoniae; Vaccination