Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Proteins.

() is a prominent mucosal pathogen causing acute otitis media (AOM). We studied nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of (30 vs. 22%,  = 0.0003) and -caused AOM rates (49 vs. 24%,  < 0.0001) than NOP children. Natural acquisition of mucosal antibodies to proteins OMP CD (IgG,  < 0.0001), OppA (IgG,  = 0.018), Hag (IgG and IgA, both  < 0.0001), and PilA2 (IgA,  < 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag ( = 0.039) and PilA2 ( = 0.0076), and IgA to OMP CD ( = 0.010), OppA ( = 0.030), and PilA2 ( = 0.043) were associated with lower carriage of in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD ( = 0.0070) and Hag ( = 0.0003), and IgA to Hag ( = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%,  < 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to -caused AOM. Enhancing antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children.