Synthetic immunomodulators and synthetic vaccines.

Efforts have been made for several years to obtain well-defined, nontoxic adjuvants and antigens which could be used for human vaccination and immunostimulation. Among synthetic adjuvants, MDP represents one of the most studied family of compounds. This molecule is the minimal active structure of whole Mycobacteria and has been shown to be endowed with numerous biological activities. MDP is adjuvant active, increases nonspecific resistance against infectious challenges and, under certain conditions, increases resistance against tumor grafts. Moreover, MDP has other pharmacological properties such as pyrogenic and somnogenic activities. Several hundred MDP derivatives have been synthetized and some of the biological activities have been dissociated. One MDP derivative presently under clinical trials has been shown to be adjuvant active but is devoid of pyrogenicity. The mechanisms of activity of these MDP and derivative molecules will be discussed. More recently, synthetic antigens which are copies of natural epitopes, have been shown to induce protective antibodies against bacterial or viral pathogens. These synthetic antigens conjugated to synthetic carriers or to synthetic adjuvants such as MDP, may permit the preparation of totally synthetic vaccines.