Induction of effective immunity to Moloney murine sarcoma virus using monoclonal anti-idiotypic antibody as immunogen.

We have isolated an anti-idiotypic mAb (RS1.1.3), which recognizes an idiotope present on several IgM mAb specific for Moloney murine leukemia virus (M-MuLV)-determined cell surface Ag. The binding of RS1.1.3 to idiotypic antibody could be inhibited by specific Ag. Intraperitoneal immunization of mice with purified RS1.1.3 antibody-induced effective immunity against Moloney murine sarcoma virus challenge. A single injection of RS1.1.3 7 days before virus challenge resulted in a 27% reduction in tumor load compared to non-immune control mice challenged with the same dose of virus, whereas multiple injections of RS1.1.3 before virus challenge resulted in a 75% reduction in tumor load. The protective effect of anti-idiotype immunization appeared to be T dependent, because immunization of athymic mice had no effect on their susceptibility to tumor virus challenge. Administration of the anti-idiotypic antibody after virus inoculation caused an increase in tumor load of nearly 50% compared to non-immune controls. BALB/c mice immunized with RS1.1.3 developed anti-anti-idiotypic antibodies, as well as M-MuLV Ag-specific antibodies. Analysis of sera from RS1.1.3-immune mice subsequently challenged with Moloney murine sarcoma virus indicated an inverse relationship between tumor load and M-MuLV-specific serum IgG titers induced by the RS1.1.3 immunization. These results indicate that anti-idiotypic mAb may be used as immunogen to induce Ag-specific antibody responses, and to cause effective immunity to a retro-virus-induced tumor.