AUTHOR=Ren Dabin , Murphy Timothy F. , Lafontaine Eric R. , Pichichero Michael E. 

TITLE=Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Moraxella catarrhalis Proteins

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00953

DOI=10.3389/fimmu.2017.00953

ISSN=1664-3224

ABSTRACT=<p><italic>Moraxella catarrhalis</italic> (<italic>Mcat</italic>) is a prominent mucosal pathogen causing acute otitis media (AOM). We studied <italic>Mcat</italic> nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate <italic>Mcat</italic> 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 <italic>Mcat</italic> (30 vs. 22%, <italic>P</italic> = 0.0003) and <italic>Mcat</italic>-caused AOM rates (49 vs. 24%, <italic>P</italic> &lt; 0.0001) than NOP children. Natural acquisition of mucosal antibodies to <italic>Mcat</italic> proteins OMP CD (IgG, <italic>P</italic> &lt; 0.0001), OppA (IgG, <italic>P</italic> = 0.018), Hag (IgG and IgA, both <italic>P</italic> &lt; 0.0001), and PilA2 (IgA, <italic>P</italic> &lt; 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag (<italic>P</italic> = 0.039) and PilA2 (<italic>P</italic> = 0.0076), and IgA to OMP CD (<italic>P</italic> = 0.010), OppA (<italic>P</italic> = 0.030), and PilA2 (<italic>P</italic> = 0.043) were associated with lower carriage of <italic>Mcat</italic> in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD (<italic>P</italic> = 0.0070) and Hag (<italic>P</italic> = 0.0003), and IgA to Hag (<italic>P</italic> = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of <italic>Mcat</italic> NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%, <italic>P</italic> &lt; 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to <italic>Mcat</italic> proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to <italic>Mcat</italic>-caused AOM. Enhancing <italic>Mcat</italic> antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children.</p>