The objective of the proposed research is to demonstrate that vaccines made from small portions (peptides) of outer membrane (OM) proteins of pathogenic bacteria can elicit productive immune responses. Towards the end, procedures have been developed which allow for the identification, purification, and subfractionation of OM proteins of Neisseria gonorrhoeae. Immunologically active regions (epitopes) can now be located within the OM protein molecules and peptides containing these regions isolated for further immunological, structural, and sequencing analyses. Immunization with these peptides should elicit both antibody (humoral) and cell-mediated (cellular) immune responses which may enhance the host's ability to resist infection. Development of these procedures has been accomplished while studying the major OM protein (PI) of N. gonorrhoeae. Studies will focus on the PI structural class associated with desseminated gonococcal infection (DGI). If peptides of this molecule, or others, are to find use as vaccines, appropriate immunological procedures, which assess both humoral and cellular responses to peptides, must be developed. The research proposed here addresses the development of assays which will allow for the thorough analyses of immune responses to peptide vaccines. These assays may also provide non-invasive (beyond blood drawing) procedures to study human immune responses to N. gonorrhoeae and, in the future, to study human responses to peptide vaccines. The development of vaccines to prevent gonorrhea has proven to be an extremely difficult problem. They may reflect the variability of the predominant OM proteins both within and among the multitude of strains of N. gonorrhoeae. Therefore, as part of this project, other OM molecules and bacterial fractions will be studied to determined their potential as vaccine components. Information gained by these studies, not only regarding the development of vaccines, but about the basic biology of N. gonorrhoeae (e.g. what accounts for serum resistance?) will surely help us to understand how this bacterium causes infection and how we can successfully control this widespread sexually transmitted disease.
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