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Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to
Dabin Ren1, Timothy F Murphy2, Eric R Lafontaine3
1Rochester General Hospital Research Institute, Rochester, NY, United States.
Abstract:
Moraxella catarrhalis (Mcat) is a prominent mucosal pathogen causing acute otitis media (AOM). We studied Mcat nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate Mcat 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 Mcat (30 vs. 22%, P = 0.0003) and Mcat-caused AOM rates (49 vs. 24%, P < 0.0001) than NOP children. Natural acquisition of mucosal antibodies to Mcat proteins OMP CD (IgG, P < 0.0001), OppA (IgG, P = 0.018), Hag (IgG and IgA, both P < 0.0001), and PilA2 (IgA, P < 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag (P = 0.039) and PilA2 (P = 0.0076), and IgA to OMP CD (P = 0.010), OppA (P = 0.030), and PilA2 (P = 0.043) were associated with lower carriage of Mcat in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD (P = 0.0070) and Hag (P = 0.0003), and IgA to Hag (P = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of Mcat NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%, P < 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to Mcat proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to Mcat-caused AOM. Enhancing Mcat antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children.
Insights
Stringently otitis prone children exhibit reduced mucosal antibody responses to Moraxella catarrhalis (Mcat) proteins, leading to higher rates of nasopharyngeal colonization and acute otitis media (AOM). Enhancing these immune responses is crucial for AOM prevention in these children.
Area of Science:
- Immunology
- Microbiology
- Pediatrics
Background:
- Moraxella catarrhalis (Mcat) is a major cause of acute otitis media (AOM), particularly in children.
- Stringently otitis prone (sOP) children experience a higher burden of AOM compared to non-otitis prone (NOP) children.
Purpose of the Study:
- To investigate Mcat nasopharyngeal (NP) colonization, AOM frequency, and mucosal antibody responses to four vaccine candidate proteins in sOP versus NOP children.
- To identify associations between mucosal antibody levels and Mcat colonization or AOM development.
Main Methods:
- Comparative study of sOP and NOP children.
- Measurement of Mcat NP colonization rates and AOM incidence.
- Quantification of mucosal antibodies (IgG and IgA) against Mcat outer membrane protein CD (OMP CD), oligopeptide permease A (OppA), hemagglutinin (Hag), and Pilin A clade 2 (PilA2).
Main Results:
- sOP children showed higher Mcat NP colonization (30% vs. 22%) and AOM rates (49% vs. 24%) than NOP children.
- Natural acquisition of antibodies to OMP CD, OppA, Hag, and PilA2 was lower in sOP children.
- Higher specific antibody levels were associated with lower Mcat carriage in NOP children and reduced progression from colonization to AOM in NOP compared to sOP children.
Conclusions:
- sOP children have a diminished mucosal antibody response to key Mcat proteins, correlating with increased colonization and AOM.
- Current natural immune responses are insufficient for AOM prevention in sOP children.
- Vaccine strategies should aim to enhance Mcat-specific mucosal immunity beyond levels achieved through natural exposure.
