title: Immune responses to pneumococcal pilus RrgA and RrgB antigens and their relationship with pneumococcal carriage in humans.
abstract: OBJECTIVE
  Pneumococcal pilus antigens are shown to be important in pneumococcal pathogenesis and induce protective immunity in animal studies, but data in humans are limited. We aimed to investigate serum and mucosal immune responses to pilus-1 proteins (RrgA and RrgB) and their relationship with pneumococcal carriage in humans.
  
  
  METHODS
  Serum and salivary antibodies to RrgA and RrgB in children and adults were analysed by ELISA and immunoblotting. Induction of B cell antibody responses to RrgA and RrgB in nasopharynx-associated lymphoid tissue was studied by ELISpot assay following stimulation with pneumococcal culture supernatants containing pilus proteins.
  
  
  RESULTS
  Significant levels of serum anti-RrgA and -RrgB antibodies were observed, and anti-RrgA antibody appeared to develop earlier in childhood. Importantly, anti-RrgA IgG titres in both serum and saliva were shown to be higher in culture-negative children than in those who were culture-positive for Streptococcus pneumoniae. Stimulation of adenotonsillar cells with pneumococcal culture supernatant induced significant RrgA- and RrgB-specific antibody secreting cells and antibody production.
  
  
  CONCLUSIONS
  Pneumococcal pilus antigens, particularly RrgA, seem to induce significant serum and mucosal antibody responses that may contribute to natural immunity against pneumococcal carriage in children.
authors: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, UK.
authors: Muhammad S
authors: MS
authors: Ahmed
authors: ENT Department, Alder Hey Children's Hospital, Liverpool, UK.
authors: Stephen
authors: S
authors: Derbyshire
authors: Institute of Translational Medicine, University of Liverpool, UK.
authors: Brian
authors: B
authors: Flanagan
authors: ENT Department, Alder Hey Children's Hospital, Liverpool, UK.
authors: Christopher
authors: C
authors: Loh
authors: ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK.
authors: Max
authors: M
authors: McCormick
authors: Novartis Vaccines and Diagnostics, Sienna, Italy.
authors: Michele
authors: M
authors: Barocchi
authors: Novartis Vaccines and Diagnostics, Sienna, Italy.
authors: Vega
authors: V
authors: Masignani
authors: Institute of Child Health, University of Bristol, UK.
authors: Adam
authors: A
authors: Finn
authors: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, UK. Electronic address: qibo.zhang@liv.ac.uk.
authors: Qibo
authors: Q
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002353:Carrier State / Q000276:immunology* / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D012463:Saliva / Q000276:immunology; D044967:Serum / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification*; D037521:Virulence Factors / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C579340:RrgA protein, Streptococcus pneumoniae; D037521:Virulence Factors; D036781:Fimbriae Proteins
keywords: B cell response; Nasopharynx-associated lymphoid tissue (NALT); Pilus proteins; Pneumococcal carriage; Serum antibody; Streptococcus pneumoniae