GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3.
The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the 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 unaffected. 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-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.
Livingston
P O
PO
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Calves
M J
MJ
Helling
F
F
Zollinger
W D
WD
Blake
M S
MS
Lowell
G H
GH
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D008081:Liposomes; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D005732:Gangliosides; D007075:Immunoglobulin M; D008081:Liposomes; C026226:ganglioside, GD3