The overall 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 that 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 humoral and cell-mediated immune responses which may enhance the host's ability to resist infection. The proposed research has three main thrusts. The first is to examine the structure of the major OM protein (PI to identify unique and conserved regions both within the PIA and PIB subgroups and between the subgroups with the long-term goal of developing peptide vaccines. The second is to establish which surface structures correlate with the bacteria's ability to resist killing by both normal human serum and by antibody-mediated complement lysis. Since a successful vaccine must elicit a protective immune response such as antibody-mediated complement killing, a fuller understanding of serum resistance will be helpful in selecting vaccine molecules and in evaluating their effectiveness. The third goal involves the further development of protein structural and immunological analyses as well as developing new protein and peptide purification systems using several high-performance liquid chromatography (HPLC) technologies. Clearly, the identification of critical OM molecules, techniques of purification, subfractionation, and characterization of these molecules, and generation of large quantities of such molecules for further study will not only provide basic information regarding the immunobiology of N. gonorrhoeae but will also be invaluable in the quest for prophylactic therapies to prevent gonorrhea.
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