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Moraxella catarrhalis is an important cause of bacterial otitis media, and a vaccine to prevent this disease would be highly desirable. Analysis of the dominant antigens on the surface of M. catarrhalis recognized by the human immune response to infection might aid in such a search. Such analysis would be most informative when studied in the eventual target age group for the vaccine; thus we have studied the immune response to M. catarrhalis in infants with otitis media.Eighteen infants (mean age, 9.4 months) experiencing an episode of otitis media caused by M. catarrhalis were studied. Acute and convalescent antibody responses were studied by whole cell enzyme-linked immunosorbent assay (heterologous strain) and by immunoblotting of outer membrane proteins (OMPs).Specific IgG was detected in 17% of acute serum samples and in 61% of convalescent sera. A rise in specific IgG was detected in 10 of 12 (83%) children 8 months of age or older, compared with 1 of 6 (17%) in younger patients (P = 0.0128). Immunoblotting revealed antibody binding to several OMPs with some detectable cross-reactivity. Four dominant OMP targets were identified, corresponding to UspA, TbpB, CopB and a ∼60-kDa protein.A combination of antigens might form the most suitable basis for a M. catarrhalis vaccine designed to prevent otitis media in this age group.