Biological mimicry of antigenic stimulation: analysis of the in vivo antibody responses induced by monoclonal anti-idiotypic antibodies.

In this study, the induction of protective antibodies against a bacterial pathogen in mice was used as a model for idiotype vaccine development. The antibody responses induced in different strains of mice by the hapten phosphorylcholine (PC) coupled to ovalbumin, PC-OVA, were compared with the responses induced by carrier conjugates of two different anti-idiotopic antibodies. One anti-idiotope, 4C11, exhibits the characteristics of an internal image of phosphorylcholine, and therefore is classified as an Ab2 beta; the other, F6, does not mimic antigen, and therefore is classified as an Ab2 alpha. The analysis of the temporal kinetics of the IgM and IgG1 anti-PC responses induced by nominal and idiotope antigens revealed dynamic responses characterized by changes in the quality and quantity of the antibody populations during the course of the immune response. All three antigens could stimulate antibodies that were PC-specific and T15 idiotope-positive in BALB/c and A/St mice. The highest titre of T15+ anti-PC antibodies was achieved with an immunization protocol which involved priming with Ab2 alpha followed by challenge with PC-OVA. Antibodies specific for the extended hapten, diazophenylphosphorylcholine, and hapten-carrier bridge determinants were being stimulated late in the responses to PC-OVA. BALB-c, A/St and CBA/N (Xid) mice all produced, late in the response to Ab2 alpha, high T15+ antibody titres which do not bind PC. The induction of T15+, non-PC binding, antibody suggests that T15 is a regulatory idiotope, expressed on antibodies having differing antigenic specificities. With regard to vaccine development, these results support the contention that effective induction of antibodies does not depend on stimulating a unique idiotope but can be achieved by anti-idiotypes reacting with different idiotopes. In addition, these results suggest that the combined use of idiotope and nominal antigens in an immunization protocol may provide the maximal protective immunity.