Polyclonal anti-idiotypes induce antibody responses protective against ricin cytotoxicity

Protein G-purified goat anti-ricin IgG, previously demonstrated to protect against ricin toxicity in vitro and in vivo, was used to raise BALB/c mouse and New Zealand White rabbit polyclonal anti-idiotypic antibodies. The generated anti-idiotypic sera were repeatedly absorbed over agarose conjugated to normal goat immunoglobulins, and purified by protein A-agarose affinity chromatography. Immunization of BALB/c mice with BALB/c anti-idiotypes did not result in a significant anti-ricin antibody response. However, injection of BALB/c mice with BALB/c anti-idiotypes conjugated to keyhole limpet haemocyanin (KLH) or with unconjugated rabbit anti-idiotypes resulted in specific and anti-ricin immune responses. The anti-idiotype-induced anti-ricin antibody responses protected against the in vitro cytotoxicity of ricin, a potent plant-derived protein synthesis inhibitor, as assessed by the murine EL-4 leukaemia cell assays. Thus, anti-idiotype-based vaccines may represent an alternative, safe and effective means of inducing protective immunity against toxins such as ricin, whose extreme in vivo toxicity render them unsafe as immunogens.