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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.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.Sixty-six patients were studied. The rates of M. catarrhalis colonization by culture, reverse transcription-PCR for uspA1 messenger RNA and uspA2 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.M. catarrhalis 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.