Antibody response after immunization with the gangliosides GM1, GM2, GM3, GD2 and GD3 in the mouse.

The gangliosides GM2, GD2 and GD3 are differentiation antigens expressed on the cell surface of human melanomas and other cancers of neuroectodermal origin. We have compared the antibody response after vaccination with gangliosides GM1, GM2, GM3, GD2 and GD3 in the mouse. Purified gangliosides were injected subcutaneously alone or attached to Salmonella minnesota mutant R595 after pretreatment of the mice with low-dose cyclophosphamide. Spontaneous GM1 antibodies, but not antibodies against the other gangliosides, were detected in many mice, the incidence increasing with age. Purified gangliosides injected alone (in saline) induced no antibody response. R595/GM1 and R595/GD3 vaccination induced consistent high-titer antibody responses. R595/GM2 and R595/GD2 induced occasional antibody responses, and R595/GM3 induced no antibody response. Comparison of the antibody responses induced against these gangliosides in the mouse with those in man reveals that GM1, GM3 and GD2 have a similar immunogenicity in both species while the relative immunogenicity of GM2 and GD3 is reversed. To understand better the basis for these differences, the antibody responses against the five gangliosides in man and the mouse were compared with their known expression in normal tissues. No correlation was detected between ganglioside expression in normal brain and immunogenicity, consistent with this being a cloistered site. The antibody responses did correlate inversely with expression in normal non-brain human and murine tissues. Variations between species of ganglioside immunogenicity may reflect variations in ganglioside expression in normal tissues.