title: Synchrony in serum antibody response to conserved proteins of Streptococcus pneumoniae in young children.
abstract: Conserved Streptococcus pneumoniae (Spn) proteins are currently under investigation as vaccine candidates. We recently identified a subset of children prone to frequent acute otitis media (AOM) that we refer to as stringently-defined otitis prone (sOP). We investigated the synchrony of serum antibody responses against 5 Spn protein vaccine antigens, PhtD, LytB, PcpA, PhtE, and PlyD1 resulting from nasopharyngeal colonization and AOM in sOP children (49 observations) and non-otitis prone (NOP) children (771 observations). Changes in serum IgG and IgM were quantitated with ELISA. IgG antibody concentrations against PhtD, PcpA, and PlyD1 rose in synchrony in sOP and NOP children; that is, the proteins appeared equally and highly immunogenic in children at age 6 to 15 months and then leveled off in their rise at 15 to 25 months. In contrast, rises in concentrations to PhtE and LytB were significantly slower and had not peaked in children even at 25 months of age, consistent with lower immunogenicity. Serum IgM responses against PhtD and PlyD1 were in synchrony in children at age 6-25 months old. PcpA did not induce a significant increase of serum IgM response in children, suggesting that primary responses to PcpA occurred prior to children attaining age 6 months old. PhtD, PcpA, and Ply elicit a synchronous natural acquisition of serum antibody in young children suggesting that a trivalent Spn protein vaccine combining PhtD, PcpA, and PlyD1 would be less likely to display antigen competition when administered as a combination vaccine in young children.
authors.affiliation: a Rochester General Hospital Research Institute ; Rochester , NY USA.
authors.forename: Dabin
authors.initials: D
authors.lastname: Ren
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Almudevar
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002353:Carrier State / Q000276:immunology; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D008297:Male; D010033:Otitis Media / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology*; D044967:Serum / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M
keywords: AOM, acute otitis media; ELISA, Enzyme-linked Immunosorbent Assay; GAM, generalized additive model; GAMM, generalized additive mixed model; LC, log10 Concentration; LME, linear mixed effects; NOP, non-otitis prone; NP, nasopharyngeal; OP, otitis prone; PCV, pneumococcal conjugate vaccine; PcpA, pneumococcal choline binding protein A; PhtD, pneumococcal histidine triad protein D; PhtE, pneumococcal histidine triad protein E; Ply, pneumolysin; PlyD1, pneumolysin derivative 1; Spn, Streptococcus pneumoniae; Streptococcus pneumoniae; generalized additive mixed model; generalized additive model; nasopharynx; pneumococcal choline binding protein A; pneumococcal conjugate vaccine; pneumococcal histidine triad protein D; pneumococcal histidine triad protein E; pneumolysin; sOP, stringently-defined otitis prone