Moraxella catarrhalis, a human mucosal pathogen, is a prominent cause of otitis media in young children and lower respiratory tract infections in adults with C.O.P.D. The significant financial burden on the health care system in this country, has stimulated research studies aimed at identifying possible vaccine components expressed on the bacterial surface. Despite these efforts, a vaccine target remains elusive. Recent studies have focused on the components of the bacterial outer membrane, as these structures would most likely be available for interaction with the host immune response. However, it is clear that very little is known about the host immune respons3e to infections with M. catarrhalis. We have reported studies demonstrating that M. catarrhalis can obtain iron from human transferrin and lactoferrin for in vitro growth, an the absence of any detectable siderophore specific proteins on the bacterial surface. We hypothesize that these proteins, named OMP B1, which binds human transferrin and LBP, which binds human lactoferrin, are likely similar to the iron-repressible, receptor proteins expressed by various Gram- negative pathogens. Using monoclonal antibodies we have shown that OMB B1 and LBP are conserved on the surface of all M. catarrhalis strains tested to date. In addition, we have shown that children recovering from otitis media have IgG antibodies to both proteins in their convalescent sera. We hypothesize that OMP B1 and LBP contain conserved, surface exposed epitopes which are expressed in vivo and are immunogenic in children. We further hypothesize that OMP BL and LBP are expressed in vivo in response to iron-limitation, thus making these proteins potential targets of the human immune response. The two broad goals of this proposal are to determine the specific structural arrangement of OMP B1 and the LBP and to determine if these proteins have potential value as vaccine components by analyzing the human immune response to each protein in children with otitis media. Our hypothesis will be tested by the following specific aims: (1) To develop and characterize monoclonal antibodies (MABs) directed to different epitopes of a specific transferrin receptor and a lactoferrin receptor. (2) To delineate membrane topography of each receptor and define antigenic domains. (3) To analyze and characterize the human antibody response, elicited in vivo, to each specific receptor.
