Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system

A convenient and versatile approach to the direct synthesis of a peptide-antigen matrix by the solid-phase method is described. The approach is called the multiple antigen peptide system (MAP) and it utilizes a simple scaffolding of a low number of sequential levels (n) of a trifunctional amino acid as the core matrix and 2n peptide antigens to form a macromolecule with a high density of peptide antigens of final Mr 10,000. The MAP model chosen for study was an octa-branching MAP consisting of a core matrix made up of three levels of lysine and eight amino terminals for anchoring peptide antigens. The MAP, containing both the core matrix and peptides of 9-16 amino acids, was prepared in a single synthesis by the solid-phase method. Six different MAPs elicited specific antibodies in rabbits and mice, of which five produced antibodies that reacted with their corresponding native proteins. In rabbits, the sera had a considerably higher titer of antibodies than sera prepared from the same peptides anchored covalently to keyhole limpet hemocyanin as carrier. Thus, the MAP provided a general, but chemically unambiguous, approach for the preparation of carrier-bound antigens of predetermined and reproducible structure and might be suitable for generating vaccines.