The goal of this proposal is to understand the molecular basis of the pathogenesis of Neisseria gonorrhoea with specific emphasis on two of its major outer membrane proteins called protein I and Protein III (PI & PIII). PI is the porin of Neisseria gonorrhoea and purified preparations have marked physiologic effects on human polymorphonuclear leukocytes. This antigen is a stable attribute of a particular strain and the antigenic diversity is relatively modest. It has therefore been considered a prime candidate for vaccine development and antibodies have protective effects in model systems. It is proposed that 3' and 5' deletion mutants of this protein will be engineered as well as hybrid PI proteins of two different serotypes and that these mutant proteins will be analyzed immunochemically with monoclonal antibodies to define the topology of the protein, ad the epitopes that are recognized by protective antibodies. Mutant PI proteins with altered porin function will be engineered or selected and their electrical and physiologic properties delineated. PIII is an invariant molecule and it is evident that human complement fixing IgG antibodies to PIII block the bactericidal and opsonic activity of antibodies directed to other surface antigens. It is proposed to construct 3' ad 5' deletions of this protein and analyze these immunochemically to define the topology of the protein and to identify whether epitopes involved in blocking can be distinguished from epitopes that are the target of bactericidal antibodies. If this is successful mutant PIII proteins lacking the blocking epitopes will be engineered and their vaccine potential explored.
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