Induction of antibodies reactive with GM2 ganglioside after immunization with lipopolysaccharides from Camplyobacter jejuni.
Ganglioside GM2, expressed on the surface of some human cancers, is a promising target for immune therapy, since GM2 antibodies are cytotoxic, can be induced in humans by vaccination, and the presence of GM2 antibodies is associated with a better prognosis in melanoma patients. In our efforts to induce long-lived, cytotoxic GM2 antibodies, we investigated lipopolysaccharides (LPS) containing "GM2-like" oligosaccharides. LPS were prepared from Campylobacter jejuni serotypes O:1, O:23, or O:36 (all sharing the oligosaccharide structure GalNAcbeta1-4Gal(113NeuAc)-Hex with ganglioside GM2), and tested for their ability to induce GM2-reactive antibodies. Immunization of NZW rabbits (2 animals per vaccine) with LPS from C. jejuni serotype O:1 in Freund's adjuvant resulted in production of high-titer IgG antibodies reactive with purified bovine brain GM2 in ELISA, dot-blot immune strains and immune thin-layer chromatography, and with GM2 derived from various human tumors by immune thin-layer chromatography. These rabbit antibodies bound to cancer cell lines expressing GM2 on their cell surface, as determined by mixed hemadsorption assays, mediating strong antibody-dependent cellular cytotoxicity (ADCC) with tumor cells expressing cell-surface GM2. Antibodies induced by vaccination with C. jejuni serotype O:1 were higher-titer (IgG ELISA titer > 1:60,000) than antibodies induced by immunization with purified GM2 (IgG ELISA titer > 1:200). Immunization with LPS from C. jejuni serotype O:36 resulted in production of moderately high-titer IgM and low-titer IgG GM2 antibodies. Immunization with LPS from C. jejuni serotype O:23 did not elicit GM2-reactive antibodies. No clinical symptoms were observed in animals immunized with these LPS preparations, with purified GM2 ganglioside, or with LPS derived from C. jejuni serotype O:19 (containing a GM1-like oligosaccharide). Our results indicate that lipopolysaccharides sharing carbohydrate epitopes with gangliosides may be useful immunogens for inducing antibodies to ganglioside antigens.
Ritter
G
G
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Fortunato
S R
SR
Cohen
L
L
Noguchi
Y
Y
Bernard
E M
EM
Stockert
E
E
Old
L J
LJ
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D016123:Campylobacter jejuni / Q000276:immunology*; D002240:Carbohydrate Sequence; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005678:G(M2) Ganglioside / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D014612:Vaccines / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D014612:Vaccines; D005678:G(M2) Ganglioside