Induction. of IgA Immune Responses in Nasal Mucosa by Intranasal Immunization of BALB/c Mice

Mice were immunized intranasally, orally, intratracheally, or intraperitoneally with outer membrane proteins (OMP) of Haemophilus influenzae and cholera toxin (CT), and Thl/Th2 and B cell immune responses were compared to investigate the mechanisms of mucosal immune responses in the nose and the usefulness of Intranasal immunization for inducing OMP-specific IgA responses. A combined vaccine of OMP and CT was admisistered on days 0,7, and 14. Antigen-specific antibody titers in saliva, nasal wash, bronchoalveolar lavage, and serum were determined by ELISA. On day 21, mononuclear cells isolated from nasal passage, lung, intestinal lamina propria, and spleen were analyzed by OMP-specific ELISPOT. CD4+ T cells isolated from spleen were cultured with OMP for 4 days, and the concentrations of cytokines in the culture supernatants were examined by ELISA. Following the immunization, a live bacterial suspension of the same strain as used for the preparation of OMP was inoculated into the nose, and the clearance of the bacteria from the nasal cavity was observed. Anti-OMP IgA antibody titers in saliva, nasal wash, and bronchoalveolar lavage and the numbers of OMP-specific IgA-producing cells in nasal passages were highest in mice immunized intranasally compared to the other groups of mice. Cytokine assay showed that IFN-y, IL-2, IL-5 and IL-6 were predominantly produced following intranasal immunization. In the clearance assay, significantly fewer bacteria were present in the nose of the intranasally immunized mice than in the control mice. These findings suggest that the nose is a powerful inductive and effector site for inducing IgA immune responses and that intranasal immunization enhances the clearance of pathogenic bacteria from the nose.