Adjuvants have been utilized to increase the immunogenicity of vaccines for over 50 years and their continued development is critical as there are a number of potential protective antigens that lack immunogenicity. Difficulties encountered with the use of adjuvants include 1) the induction of adequate quantities of antibodies to a certain antigen which are not protective, 2) toxicity of the adjuvant itself and 3) absence of immunopotentiating ability of potential adjuvants for certain antigens. We are interested in the use of Neisserial porins as adjuvants. Previous work has shown that they can be highly immunogenic in the absence of other adjuvants. Moreover, Neisserial porins when formed into proteosomes have been used as adjuvants for non-immunogenic antigens. The studies described in this grant are designed to explore the immunostimulatory effect of Neisserial porins and possible reasons for this phenomenon. We want to investigate the mechanism of their immune stimulatory ability because this might help define the antigens these porins can aid. The use of Neisserial porins as adjuvants has many distinct advantages 1) they can be easily purified close to homogeneity, 2) they are easily obtained in large quantities from Neisserial strains and 3) they have minimal toxicity as evidenced in multiple animal trials and in preliminary human trials. A model system will be employed to test their adjuvanticity. This system will examine two different types of test antigens which will be non- covalently complexed with the porins. The first is a T cell dependent antigen, an oligopeptide derived from the gene 3 protein (attachment protein) of the filamentous coliphages (f1, fd and M13). This antigen will test the ability of Neisserial porins to augment the immune response towards a peptide, which is normally difficult to obtain. The second antigen is a T cell independent antigen, group C meningococcal capsular polysaccharide (C-CPS) and will test the ability of Neisserial porins to alter a T cell independent immune response to a T cell dependent response. The ability of both gonococcal and meningococcal porins to increase the quantity, quality and longevity of anti-g3p peptide and anti-C-CPS antibody production will be examined. the level of anti-g3p peptide and anti-C-CPS antibodies will be correlated to the T cell response towards Neisserial porins in order to investigate if the immunopotentiating ability of these porins is related to their ability to stimulate T cells. All these investigations would help define the adjuvant ability and immunogenicity of Neisserial porins.
| Wetzler, L M; Ho, Y; Reiser, H et al. (1996) Neisserial porins induce B lymphocytes to express costimulatory B7-2 molecules and to proliferate. J Exp Med 183:1151-9 |
