title: Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children.
abstract: OBJECTIVE
  We previously found that nasopharyngeal (NP) colonization by Streptococcus pneumoniae elicits mucosal antibody responses to three protein vaccine candidates: pneumococcal histidine triad protein D (PhtD), pneumococcal choline-binding protein A (PcpA), and detoxified pneumolysin (PlyD1). Here we sought to determine if mucosal antibody levels to the proteins correlated with protection from acute otitis media (AOM) and NP colonization.
  
  
  METHODS
  A total of 228 NP samples were prospectively collected from 100 healthy infants at 6-24 months of age. Whenever children were diagnosed with AOM, middle ear fluids were collected to confirm the diagnosis by microbiological culture. NP mucosal IgG and IgA were quantified by ELISA.
  
  
  RESULTS
  Higher NP mucosal antibody levels to S. pneumoniae proteins correlated with significantly decreased likelihood of developing AOM caused by S. pneumoniae during 3 to 12 months of subsequent prospective monitoring. Specifically, children who did not experience AOM (n=111samples) caused by S. pneumoniae had two- to five-fold higher mucosal IgG levels to PcpA (all p values <0.01), six- to eight-fold higher IgA to PhtD (all p values <0.05); two- to three-folder higher IgA to PcpA (all p values <0.05), and two- to three-fold higher IgA to PlyD1 (p 0.08, p 0.03 and p 0.08) compared with children who did experience AOM (n=18samples). No association between mucosal antibody levels to the three proteins and NP colonization with S. pneumoniae was found.
  
  
  CONCLUSIONS
  Higher NP mucosal IgG levels to PcpA, and IgA to PhtD, PcpA and PlyD1 correlate with reduced risk of development of S. pneumoniae AOM infection but not with reduced risk of NP colonization in young children.
authors.affiliation: Rochester General Hospital Research Institute, Rochester, NY, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Legacy Pediatrics, Rochester, NY, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Casey
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Almudevar
authors.affiliation: Rochester General Hospital Research Institute, Rochester, NY, USA; Legacy Pediatrics, Rochester, NY, USA. Electronic address: michael.pichichero@rochesterregional.org.
authors.forename: M E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D000907:Antibodies, Bacterial / Q000032:analysis*; D000942:Antigens, Bacterial / Q000276:immunology; D002353:Carrier State / Q000517:prevention & control*; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology*; D010033:Otitis Media / Q000517:prevention & control*; D011008:Pneumococcal Infections / Q000517:prevention & control*; D011446:Prospective Studies; D018570:Risk Assessment; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G
keywords: Acute otitis media; Mucosal antibody; Pneumococcal choline binding protein A (PcpA); Pneumococcal histidine triad protein D (PhtD); Pneumolysin (Ply); Streptococcus pneumoniae