title: Serotype-specific and age-dependent generation of pneumococcal polysaccharide-specific memory B-cell and antibody responses to immunization with a pneumococcal conjugate vaccine.
abstract: Glycoconjugate vaccines have dramatically reduced the incidence of encapsulated bacterial diseases in toddlers under 2 years of age, but vaccine-induced antibody levels in this age group wane rapidly. We immunized adults and 12-month-old toddlers with heptavalent pneumococcal conjugate vaccine to determine differences in B-cell and antibody responses. The adults and 12-month-old toddlers received a pneumococcal conjugate vaccine. The toddlers received a second dose at 14 months of age. The frequencies of diphtheria toxoid and serotype 4, 14, and 23F polysaccharide-specific plasma cells and memory B cells were determined by enzyme-linked immunospot assay. The toddlers had no preexisting polysaccharide-specific memory B cells or serum immunoglobulin G (IgG) antibody but had good diphtheria toxoid-specific memory responses. The frequencies of plasma cells and memory B cells increased by day 7 (P < 0.0001) in the adults and the toddlers following a single dose of conjugate, but the polysaccharide responses were significantly lower in the toddlers than in the adults (P = 0.009 to <0.001). IgM dominated the toddler antibody responses, and class switching to the IgG was serotype dependent. A second dose of vaccine enhanced the antibody and memory B-cell responses in the toddlers but not the ex vivo plasma cell responses. Two doses of pneumococcal conjugate vaccine are required in toddlers to generate memory B-cell frequencies and antibody class switching for each pneumococcal polysaccharide equivalent to that seen in adults.
authors.affiliation: Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, The Churchill Hospital,Oxford, Oxfordshire, United Kingdom. elizabeth.clutterbuck@paediatrics.ox.ac.uk
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Clutterbuck
authors.forename: Sarah
authors.initials: S
authors.lastname: Oh
authors.forename: Mainga
authors.initials: M
authors.lastname: Hamaluba
authors.forename: Sharon
authors.initials: S
authors.lastname: Westcar
authors.forename: Peter C L
authors.initials: PC
authors.lastname: Beverley
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000328:Adult; D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000276:immunology; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000276:immunology*; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines