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Mucosal immune response to specific outer membrane proteins of Moraxella catarrhalis in young children
Patricia Stutzmann Meier1, Simone Freiburghaus, Andrea Martin
1Institute for Infectious Diseases, University of Bern, Switzerland.
Background:
Moraxella catarrhalis is an important cause of otitis media. A number of candidate antigens for a future infant otitis media vaccine have been identified, but their mucosal immunogenicity induced by nasopharyngeal M. catarrhalis colonization has not been characterized. The aim of this study was to determine the salivary IgA response to M. catarrhalis outer membrane proteins (OMP) in young children.
Methods:
Children ages 1 to 24 months evaluated for acute respiratory tract infection were prospectively enrolled. M. catarrhalis nasopharyngeal colonization was determined by (1) selective culture and (2) detection by reverse transcription-PCR of messenger RNA specific for the OMP UspA1 and UspA2. Salivary IgA responses were detected by immunoblot analysis of M. catarrhalis OMP. Isogenic knockout mutants for UspA1, UspA2, hemagglutinin (Hag), transferrin-binding protein B (TbpB) and CopB were constructed for identification of specific target OMP.
Results:
Sixty-six patients were studied. The rates of M. catarrhalis colonization by culture, reverse transcription-PCR for messenger RNA and mRNA were 40, 94 and 58%, respectively. Anti-M. catarrhalis salivary IgA was detected in 62 patients (94%). IgA directed against a >250-kDa antigen (assigned to UspA1/UspA2 by mutant analysis) and a 200-kDa antigen (Hag) were detected in 65 and 70% of patients, respectively. Bands at 80 to 85 kDa (82%) consisted of IgA directed against monomeric UspA2, TbpB and CopB.
Conclusions:
colonization occurring in early infancy is associated with a consistent mucosal immune response directed against the UspA proteins, Hag and other OMP. The data suggest that several M. catarrhalis OMP are immunogens of the nasopharyngeal mucosal immune system of infants.
Insights
Infant Moraxella catarrhalis colonization triggers a strong salivary IgA immune response against key outer membrane proteins (OMP). This finding is crucial for developing effective otitis media vaccines targeting young children.
Area of Science:
- Immunology
- Microbiology
- Pediatrics
Background:
- Moraxella catarrhalis is a significant pathogen causing otitis media in infants.
- The mucosal immunogenicity of candidate vaccine antigens during nasopharyngeal colonization remains uncharacterized.
Purpose of the Study:
- To investigate the salivary IgA immune response to M. catarrhalis outer membrane proteins (OMP) in young children.
- To identify specific M. catarrhalis OMP targets of the infant mucosal immune system.
Main Methods:
- Prospective enrollment of children aged 1-24 months with respiratory tract infections.
- Detection of M. catarrhalis colonization via culture and RT-PCR for UspA1/UspA2 mRNA.
- Analysis of salivary IgA responses to M. catarrhalis OMP using immunoblotting and isogenic mutants.
Main Results:
- High rates of M. catarrhalis colonization (up to 94%) were observed.
- Salivary IgA against M. catarrhalis OMP was detected in 94% of patients.
- Specific IgA responses targeted UspA1/UspA2, hemagglutinin (Hag), TbpB, and CopB.
Conclusions:
- Nasopharyngeal colonization in infancy elicits a robust mucosal immune response against multiple M. catarrhalis OMP.
- Several M. catarrhalis OMP are identified as immunogens in the infant nasopharyngeal mucosal immune system.
- These findings support the development of OMP-based vaccines for infant otitis media.