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.

A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media

“…Pneumolysin toxoids are an attractive vaccine candidate, because this factor is highly conserved in pneumococci (43) and tissue damage resulting from the action of the toxin is responsible for many disease symptoms (44). Additionally, immunity against pneumolysin is raised during natural infection (45), suggesting that it is available to the immune system during infection. Pneumolysin is especially relevant in protection against otitis, as it can directly cause cochlear damage and hearing loss in animal models (46), suggesting that a neutralizing antibody could protect against this sequela of AOM.…”

“…Pneumolysin is especially relevant in protection against otitis, as it can directly cause cochlear damage and hearing loss in animal models (46), suggesting that a neutralizing antibody could protect against this sequela of AOM. Additionally, levels of antipneumolysin antibody have been correlated with reduced incidence of pneumococcal AOM in children (45).…”

Serum antibody response to Moraxella catarrhalis proteins in stringently defined otitis prone children

“…Although they have not studied Mcat proteins, we note that studies by the group led by Thornton and Richmond involving Australian children who experience recurrent AOM have not observed lower antibody responses to Spn proteins or capsular polysaccharides or to NTHi proteins. [38][39][40] However there are important differences in the two study populations. We study stringently-defined otitis prone (sOP) children who have every clinical diagnosis confirmed by tympanocentesis and every otopathogen identified by culture, while the Australian study population is diagnosed clinically by health care providers not directly involved in the research and in some cases middle ear fluid obtained from ruptured eardrums.…”

“…We study stringently-defined otitis prone (sOP) children who have every clinical diagnosis confirmed by tympanocentesis and every otopathogen identified by culture, while the Australian study population is diagnosed clinically by health care providers not directly involved in the research and in some cases middle ear fluid obtained from ruptured eardrums. [38][39][40] Also only 26% of our sOP children require ventilation tubes (unpublished data) while all of the Australian OP children studied for antibody responses to protein antigens were recruited at time of ventilation tube surgery. [38][39][40] Moreover, they found that Australian aboriginal (possibly similar to OP) children with otitis media displayed lower serum IgG to NTHi but not Spn proteins than non-aboriginal (possibly similar to NOP) or healthy children.…”

“…[38][39][40] Also only 26% of our sOP children require ventilation tubes (unpublished data) while all of the Australian OP children studied for antibody responses to protein antigens were recruited at time of ventilation tube surgery. [38][39][40] Moreover, they found that Australian aboriginal (possibly similar to OP) children with otitis media displayed lower serum IgG to NTHi but not Spn proteins than non-aboriginal (possibly similar to NOP) or healthy children. [41] Consistent with our findings, these observations also suggest that OP children in different geographic areas may have similar defects in producing serum antibodies to certain otopathogens.…”