GD3 PROTEOSOME VACCINES INDUCE CONSISTENT IGM ANTIBODIES AGAINST THE GANGLIOSIDE GD3/

The gangliosides of melanoma and other tumours of neuroectodermal orig in are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guerin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delive ry system, proteosomes, which is especially effective. Highly hydropho bic Neisserial outer membrane proteins (OMP) form multimolecular lipos ome-like vesicular structures termed proteosomes which can readily inc orporate amphiphilic molecules such as GD3 ganglioside. The optimal GD 3/proteosome vaccine formulation for induction of GD3 antibodies in th e mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaf fected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-s urface gangliosides. The demonstrated safety of meningococcal OMP in h umans and the data in mice presented here suggest that proteosome vacc ines have potential for augmenting the immunogenicity of amphipathic t umour antigens in humans.