USE OF SEQUENTIAL OLIGOPEPTIDE CARRIERS (SOCN) IN THE DESIGN OF POTENT LEISHMANIA GP63 IMMUNOGENIC PEPTIDES

The antigenic sequence (250-257) Ac-IASRYDQL (gp63-SRYD) of the major surface glycoprotein of leishmania, gp63, was covalently attached to t he Lys-(NH2)-H-E groups of a new sequential oligopeptide carrier (SOCn ), namely; (Lys-Aib-Gly)(n) (n=5,6), in order to obtain potent immunog ens and sire-specific antibodies. It was shown, using H-1-NMR spectros copy; that the gp63-SRYD, octapeptides bound to the SOCn retain their original structural profile outlined by an ionic interaction between R and D side chains and a type I beta-turn involving the QNH --> RCO hy drogen bonding Also, the gp63-SRYD octapeptides linked to the carrier do not experience conformational restrictions, probably because of the favorable conformation of the SOCn. Immunizations of outbred rabbits with the peptide carriers designed resulted in high-titered antibody r esponse to the gp63-SRYD octa-peptide and the gp63 cognate protein. Th us, this chemically defined model may be used for incorporating ''prot ective'' Leishmania epitopes and ultimately for the design of a multiv alent synthetic vaccine against leishmaniosis.