Idiotypic vaccinations: consideration towards a practical application.

Abstract

We review the theoretical background as well as the available experimental data in animals and man on the possible use of anti-idiotypic antibodies as vaccines for the prevention of infectious diseases. In the first part, the basic experiments and concepts that fostered the idea of idiotypic vaccination are discussed. Although many basic aspects are still unknown, we conclude that the immune system can take antibody variable domains as representatives ("semiotypes") of foreign antigens not only in special cases, but also in a general sense. Among the major areas to be studied further are the events that regulate response to antibody in relation to those that regulate responses to antigen. Initial experiments suggest that responses to antibody may be directed intentionally towards a desired outcome. In the second part, we evaluate the actual medical need for idiotypic vaccination. We conclude that most novel vaccination regimes are likely to be developed with the help of protein chemistry and gene technology. Idiotypic vaccines may become applicable only in special, well-defined situations, such as cases of nonresponsiveness to antigen or cases of severe dysregulation of immunity by the antigen. The third part of the article deals with experimental models for idiotypic vaccination. A number of groups have performed protection experiments in various model infections of experimental animals using anti-idiotypic antibodies as vaccines. In a fair number of cases, involving infections with viral, bacterial, and parasitic microorganisms, protection has been successfully induced. In the fourth part, we summarize studies on idiotype expression in human antigen-driven immune responses. The limited data available suggest that human idiotype expression follows similar rules as in experimental animals. In particular, widely cross-relative idiotopes are readily detected using monoclonal anti-idiotopes. Antibodies to such idiotopes reacted with major proportions of the antibodies of a given specificity. Taken together, many factors point towards the feasibility of idiotypic vaccination.