Nontypable Haemophilus influenzae (NTHI) is now well established as an important pathogen in adults and children. This bacterium causes pneumonia, bacteremia, meningitis, post-partum sepsis and acute febrile tracheobronchitis in adults. In addition, NTHI causes neonatal sepsis and is a frequent etiologic agent in acute otitis media in infants and children. With the recognition of NTHI as a human pathogen, studies are planned to understand the pathogenesis and epidemiology of infection due to this bacterium. This proposal will focus on outer membrane proteins (OMP) of NTHI. The proposed studies can be divided into two major approaches. In the first part (Specific Aim 1) work will focus on antigenic differences of OMP's among strains of NTHI. These antigenic differences will be used to form the basis of a serotyping system for NTHI based on OMP's. The second major approach (Specific Aim 2) will focus on common antigens of OMP's among strains of NTHI. We will identify OMP's which are a) surface-exposed, b) targets of human antibody, and c) common to many strains of NTHI. These OMP's will be further characterized by studying their surface-exposed peptides and the role of these OMP's and peptides in human immunity to NTHI infection. 1. Using an OMP serotyping system based on polyclonal serum as a foundation, we will develop a serotyping system by identifying monoclonal antibodies directed against serotype-specific determinants on OMP's. Once this system is developed, we will study a collection of epidemiologically well-defined strains of NTHI to determine the distribution characteristics of these determinants among disease and carrier isolates. 2. Surface-exposed epitopes on OMP's will be identified and characterized. We will focus on OMP's which are common to many strains of NTHI and which are targets of human antibody. The surface-exposed peptides will be identified and synthesized. The OMP's will be isolated. The role of the OMP's and peptides as targets of human bactericidal antibody will be assessed.
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