Role of muramyl peptides for the enhancement of synthetic vaccines.

Adjuvants are largely used in human and veterinary medicine with conventional vaccines. Vaccines of the future could be synthetic immunogens which would require the addition of more immunomodulators. Muramyl peptides (MDP) are synthetic glycopeptides which can substitute mycobacteria in FCA and are also adjuvant-active in saline. A derivative, Murabutide, is currently undergoing clinical trials and has been found efficient in several experimental models of conventional and synthetic vaccines. For example, when a Plasmodium knowlesi sporozoite peptide conjugated to tetanus toxoid was administered in saline with Murabutide higher titers of biologically active antibodies were obtained than when the same conjugate was given in FCA. Coupling of MDP or derivatives to the immunogens enhanced their activity and allowed the use of carriers to be diminished or even avoided. In the same malarial model the linkage of a Murabutide derivative to the conjugate stimulated the response to the peptide and decreased the response to the carrier. Promising results were obtained when several peptides copying structures of different pathogens were associated in the same molecule by covalent linkage and administered with Murabutide in saline: biologically active antibodies were demonstrated to three of the corresponding pathogens.