Over the past 10 to 15 years, Moraxella (Brahamella) catarrhalis has emerged as an important human pathogen. It is common cause of otitis media in infants and children and it causes lower respiratory tract infection in adults with chronic lung disease. In order to develop methods for preventing these infections (such as vaccines), one must understand the epidemiology and pathogenesis of these infections and characterize the human immune response to the organism. To accomplish this, it will be important to learn about the surface antigens of B. catarrhalis. During the initial funding period of this project, basic studies to identify and characterize the major outer membrane proteins (OMPs) of the bacterium have been performed. Based on these studies, we have identified two OMPs which will be the focus of the studies proposed in this application.
One specific aim will focus on an antigenically conserved surface antigen while the second specific aim will focus on an antigenically heterogeneous surface antigen. CD is the major heat-modifiable OMP which is conserved among strains of B. catarrhalis. CD contains epitopes which are abundantly expressed on the surface of the intact bacterium. Our hypothesis is that antibodies to the appropriate epitopes on OMP CD will be protective and that this OMP therefore represents a potential vaccine. Experiments to test this hypothesis will include: mapping surface antigenic domains, assessing these epitopes as targets of human functional antibodies, determining the stability of these epitopes in the human respiratory tract and measuring the human immune response specifically to these surface exposed epitopes. OMP B is a major OMP which is antigenically heterogeneous among strains. Preliminary work indicates that OMP B contains surface epitopes which demonstrate a modest degree of heterogeneity among strains and that humans make antibodies to these epitopes following infection. Our hypothesis is that OMP B contains serotype antigens and that a serotyping system for B. catarrhalis can be based on the antigenic determinants of OMP B. Work proposed in the application includes the development of a monoclonal antibody based serotyping system based on surface-exposed epitopes of OMP B and the identification of the epitopes upon which the system will be based. The work proposed will lead to new information about the surface antigenic structure of this important human pathogen. Such information is a critical step in learning more about t he pathogenesis and epidemiology of infections caused by B. catarrhalis so that strategies for preventing these infections can be developed.
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