The purpose of this project is to understand pathogenesis and immunobiological properties of bacterial otitis media. In this fiscal year, efforts are focusing on investigating a new route of intra-nasal-associated lymphoid tissue (intra-NALT) administration of antigens to circumvent the antigen transportation barrier. A comparative study was carried out on mice administered with killed whole cells of Moraxella catarrhalis strain 25238 by intra-NALT injection and nasal inoculation. Both routes induced significant elevations of several isotype antibodies against strain 25238 in saliva, lung lavage, and serum as measured by an enzyme-linked immunosorbent assay. Most of these antibodies were paralleled by the numbers of their corresponding antibody forming cells in mucosal or systemic lymphoid tissues. However, intra-NALT injection elicited significantly higher levels of immunoglobulin (Ig) A and IgG in saliva, IgA, IgG and IgM in lung lavage, and IgG and IgM in sera than nasal inoculation. In addition, both routes generated significant reductions of bacteria in lungs following an aerosol challenge with strain 25238 in a mouse model of pulmonary clearance. Once again, intra-NALT injection showed better bacterial clearance in mouse lungs than nasal inoculation. These results demonstrate that intra-NALT administration of antigens is a convenient, noninvasive, and effective route for mucosal immunization that elicits improved mucosal and systemic immunity. This new route can be used as a model to study mucosal antigens or vaccine candidates in terms of antigen activation and interaction with the NALT that is one of major inductive sites for common mucosal immune system.
