Neisseria gonorrhoeae infects up to half a million people yearly in the US, causing a variety of diseases. Treatment of these diseases costs billions of dollars each year. Furthermore, inflammation from gonococcal infection increases the risk of transmitting and acquiring other sexually transmitted disease agents such as HIV. Despite a pressing need and decades of active research, an effective gonococcal vaccine has yet to be developed. One of the barriers to a gonococcal vaccine is the extraordinary variation of the most abundant and immunodominant gonococcal surface components. There may be less abundant surface molecules that are invariant. Recombinant DNA methods make it practical to develop subunit vaccines that focus immune responses to these less abundant, invariant molecules. The goal of this application is to evaluate the subunit vaccine potential of a particularly promising 85kDA outer membrane protein (OMP85) of Neisseria gonorrhoeae. Preliminary data indicated that Omp85 was invariant and universally expressed in tested strains. Antibodies to Omp85 homologues protected against infection with Haemophilus influenzae and Pasteurella multocida. The hypotheses to be tested are that Omp85 is invariantly and universally expressed in N. gonorrhoeae and that antisera directed against Omp85 are bactericidal and interfere with gonococcal adherence to, and/or penetration of, human epithelial cells. The following specific aims will test the hypotheses: (1) the variability of Omp85 among gonococcal strains will be determined. (2) Immunological characteristics of Omp85 will be evaluated. (3) Surface reactive antibodies to Omp85 will be used in bactericidal and cell adherence/invasion assays to determine if anti-Omp85 antibodies are bactericidal and if they interfere with gonococcal-host cell interactions. Completion of the specific aims will demonstrate the vaccine potential of Omp85. If the hypotheses are supported then Omp85 may be a valuable vaccine molecule similar to the related protective antigens in H. influenzae and P. multocida.