Non-typeable Haemophilus influenzae (NTH1) is a common cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. Outer membrane protein P6 is a 16 kDa lipoprotein which is present in all strains of MTH1. The P6 protein is highly conserved among strains of NTH1, an important characteristics of a vaccine antigen. A large body of evidence from experimental animal models and from studies of the human immune response indicate that antibodies to P6 are protective against infection due to NTH1. In view of these observations, there is substantial interest in testing P6 as a vaccine to prevent infections caused by NTH. We have characterized the T cell response to P6 and the precise location of an immunodominant T cell epitope has been identified. This T cell epitope elicits P6 specific responses in mice of several different MHC Class II haplotypes. We have also demonstrated the ability of this T cell epitope to provide functional help to a B cell epitope in generating P6 specific antibodies. We now propose to study in vitro human T cell responses to P6 and synthetic peptides which span the entire sequence of the mature native protein. In an effort to elucidate the human antibody response to immunization with P6, SCID mice will be reconstituted with human peripheral blood lymphocytes, immunized with P6 antigens and the immun response will be characterized. Lymphocytes from normal adults and adults with COPD will be studied. The proposed studies will provide important information regarding human immune responses to the P6 protein and will further our knowledge regarding the potential of P6 as a vaccine antigen. Finally we will explore the potential of antigen delivery by the oral route and determine the ability of P6 and its peptides to generate both mucosal and systemic antibody responses.
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