The goal of this investigation is to study and characterize gonococcal antigens. Their role in promoting specific types of inflammation in the variety of clinical syndromes produced by N. gonorrhoeae will also be studied. Human antibodies with specificity for distinct outer membrane (OM) antigens and their derivatives will be studied for their ability to kill organisms in the presence of complement (C') (antibodies directed against LOSs and their derivatives) and in abrogating this function. OM antigens and their derivatives will be harvested and chemical and physical techniques will be used to isolate, purify and characterize the antigens. Individual OM proteins (OMP's) including PI and PIII and oligosaccharide antigens derived from LOS's will be prepared. Sensitive immunologic assays will be utilized to detect antibodies directed against important antigens. Specific interactions of gonococcal antigens with antibody and C' will be examined to characterize the effect of antigen diversity upon the different clinical syndromes produced by N. gonorrhoeae. The liposome membrane model has been adapted to the study of these interactions and will be further utilized. Gonococci will be captured directly from secretions of infected patients who have had their disease carefully classified. Monoclonal antibodies will be used for capture and organisms will then be examined for surface bound immunoglobulins and C' components by ELISA. C' component proteins, and specific antibody activity directed against LOS and OMP antigens of infecting gonococci will be measured in secretions of infected patients by ELISA. The identification of host proteins on the surface of gonococci and the measurement and characterization of these proteins in secretions will permit an assessment of the biologic mechanisms that operate in patients with different clinical manifestations of disease. This will provide an understanding of how individual hosts respond to gonococcal infection as well as how individual strains of gonococci cause unique manifestations of disease. The serologic specificity of cell wall LOS and their derivatives will also be studied in attempts to identify antibody responses to common LOS antigen determinants. Important clinical and epidemiologic questions will be answered by jointly identifying gonococcal antigens and their corresponding immunologic activity. Antigens that might elicit a protective response to infection will be identified and, if suitable, will be studied for use as a vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015633-08
Application #
3126306
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1978-12-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02118