Phae I consists of developing a gonococcal vaccine consisting of purified major outer membrane protein (Protein I) of the gonococcus. This will be a joint project with our laboratory and the NIH, and the clinical aspect of the vaccine trial will be performed at the latter. We will be developing the vaccine, testing its immunogenicity in rabbits, and evaluating the antigonococcal activity of the sera obtained. Additionally, once human sera and secretions are available from volunteers at the NIH, we will also evaluate their sera for antibody production and antigonococcal activity. Unique aspects of these experiments include utilizing gonococcal IgA protease and a recently described streptococcal protein that binds IgA with a high affinity to further delineate the IgA levels in human secretion in response to the vaccine. The remainder of my time during Phase I will be spent taking various scientific courses and tutorials specific for the tasks described above, which is outlined in the sponsor's section. Phase II consists of utilizing knowledge gained from Phase I and extending the studies of the major outer membrane protein of N. gonorrheae to Campylobacter jejuni, an invasive intestinal pathogen that only fairly recently has been discovered to be an extremely important cause of infectious diarrhea. We will look at the function of this porin, its importance in pathogenesis. The immune response to it and eventually at the genetic make-up and regulation of its production. This project is a perfect extension of the work already done in this laboratory.
|Bjerknes, R; Guttormsen, H K; Solberg, C O et al. (1995) Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but prime the neutrophils to increase their oxidative burst. Infect Immun 63:160-7|
|Guttormsen, H K; Wetzler, L M; Solberg, C O (1994) Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease. Infect Immun 62:1437-43|
|Guttormsen, H K; Wetzler, L M; Naess, A (1993) Humoral immune response to the class 3 outer membrane protein during the course of meningococcal disease. Infect Immun 61:4734-42|
|Wetzler, L M; Blake, M S; Barry, K et al. (1992) Gonococcal porin vaccine evaluation: comparison of Por proteosomes, liposomes, and blebs isolated from rmp deletion mutants. J Infect Dis 166:551-5|
|Wetzler, L M; Blake, M S; Gotschlich, E C (1989) Protein I (Por) of Neisseria gonorrhoeae as an immunogen: liposomes, proteosomes, and the lack of blocking antibodies. Trans Assoc Am Physicians 102:78-90|