title: Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides.
abstract: The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group (P< 0.05). The production of functional antipneumococcal antibodies in otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia lea-ann.kirkham@uwa.edu.au.|Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia.
authors.forename: Lea-Ann S
authors.initials: LS
authors.lastname: Kirkham
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: Selma P
authors.initials: SP
authors.lastname: Wiertsema
authors.affiliation: Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia.
authors.forename: Karli J
authors.initials: KJ
authors.lastname: Corscadden
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: Tulia
authors.initials: T
authors.lastname: Mateus
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: Gemma L
authors.initials: GL
authors.lastname: Mullaney
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.|School of Public Health, Curtin University, Perth, Australia.
authors.forename: Guicheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.|Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia.|Departments of Immunology and Paediatric Medicine, Princess Margaret Hospital for Children, Perth, Australia.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Richmond
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.|Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia.
authors.forename: Ruth B
authors.initials: RB
authors.lastname: Thornton
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000276:immunology; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D009500:Neutralization Tests; D009895:Opsonin Proteins / Q000097:blood; D010031:Otitis / Q000276:immunology*; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013301:Streptolysins / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae
keywords: Streptococcus pneumoniae; antibody function; antibody potency; neutralizing titer; opsonophagocytosis; otitis media; pneumococcal conjugate vaccine; pneumococcal polysaccharides; pneumolysin; rAOM; vaccines