title: Attachment of monophosphoryl lipid A (MPL) to cells and liposomes augments antibody response to membrane-bound gangliosides.
abstract: Antibodies to gangliosides are found in low levels in normal individuals, and attempts to augment their production have had limited success. Murine studies suggest that the antibody response to membrane-bound cryptic antigens, such as phospholipids and gangliosides, can be induced and augmented by attaching lipid A to membranes. Therefore, we assessed the ability of monophosphoryl lipid A, a non-toxic derivative of lipid A, to augment antibody response against membrane-associated gangliosides. Anti-ganglioside antibodies were IgM after the first and second immunizations; in contrast, anti-phospholipid antibodies were IgM after the first immunization and IgG after the second immunization. Mice (BALB/c) immunized with MPL-attached human cells as well as mice (C57BL/6J) immunized with MPL-attached syngeneic tumor cells (B16 melanoma) produced a significant IgM response. Mice (C57BL/6J) immunized with MPL-attached liposomes containing GM3 developed significantly higher IgM responses than those immunized with purified gangliosides, MPL or MPL-free B16 cells. However, the antibody response after immunization with MPL-GM3-liposomes is similar to that after immunization with MPL-attached tumor cells, even though the MPL-liposomes contained a 27-fold higher level of gangliosides than the tumor cells. Our results emphasize that co-expression of MPL with membrane-bound gangliosides is necessary to augment the anti-ganglioside antibody response. These findings may shed light on the elevated titers of anti-ganglioside IgM antibodies found in patients with motor neuron diseases, various neuropathies and classical ALS, and are relevant to clearance of circulating immunosuppressive gangliosides in cancer patients.
authors.affiliation: Laboratory of Glycolipid Immunotherapy, John Wayne Cancer Institute, Santa Monica, CA 90404.
authors.forename: M H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: D L
authors.initials: DL
authors.lastname: Morton
authors.forename: R F
authors.initials: RF
authors.lastname: Irie
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D008563:Membrane Lipids / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D005732:Gangliosides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D008081:Liposomes; D008563:Membrane Lipids; C048436:monophosphoryl lipid A