Induction of antibodies reactive with GM2 ganglioside after immunization with lipopolysaccharides from Campylobacter jejuni Journal Article
| Authors: | Ritter, G.; Fortunato, S. R.; Cohen, L.; Noguchi, Y.; Bernard, E. M.; Stockert, E.; Old, L. J. |
| Article Title: | Induction of antibodies reactive with GM2 ganglioside after immunization with lipopolysaccharides from Campylobacter jejuni |
| Abstract: | 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 GalNAcĪ²1-4Gal(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 stains 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. |
| Keywords: | human tissue; nonhuman; animals; mice; melanoma; animal experiment; cytotoxicity; enzyme linked immunosorbent assay; molecular sequence data; immunoglobulin g; immunogenicity; cattle; enzyme-linked immunosorbent assay; tumor vaccine; ganglioside gm2; carbohydrate sequence; antibody production; vaccines; immunoglobulin m; immunization; rabbits; campylobacter jejuni; lipopolysaccharides; rabbit; bacterium lipopolysaccharide; subcutaneous drug administration; g(m2) ganglioside; antibody-dependent cell cytotoxicity; humans; human; female; priority journal; article |
| Journal Title: | International Journal of Cancer |
| Volume: | 66 |
| Issue: | 2 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1996-04-10 |
| Start Page: | 184 |
| End Page: | 190 |
| Language: | English |
| DOI: | 10.1002/(sici)1097-0215(19960410)66:2<184::aid-ijc8>3.0.co;2-z |
| PUBMED: | 8603809 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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