Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP)

Certain gangliosides are tumor-associated antigens that constitute potentia l targets for cancer immunotherapy. A major drawback in the design of gangl ioside-based cancer vaccines, however, is the poor immunogenicity of these glycolipids. Here we report the immunological and physicochemical propertie s of very small size proteoliposomes (VSSP) obtained by using anionic deter gents to incorporate gangliosides into the outer membrane protein complex ( OMPC) of N. meningitidis. VSSP of three different gangliosides, GM3, NGcGM3 and GD3, were tested. These gangliosides differ in level of expression in normal tissues and in immunogenicity in different animal species. We show t hat the immunization with VSSP in an oil adjuvant consistently induced both IgM and IgG anti-ganglioside antibodies. In the mouse, the anti-gangliosid e IgG fraction was not restricted to the typical T-independent isotype IgG3 . Unexpectedly, significant levels of the T-dependent IgG1, IgG2a and parti cularly IgG2b were also found. VSSP-mediated enhancement of the immunogenic ity was not restricted to the relatively immunogenic ganglioside GD3, satis factory immune responses against highly tolerated GM3 and NGcGM3 were also obtained. Similar results were achieved in chickens and monkeys. No reactog enicity was observed even when self-gangliosides were used for immunization . VSSP overcame natural tolerance to gangliosides in an adjuvant dependent fashion. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.