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

TLDR

A convenient and versatile solid‑phase method for directly synthesizing a peptide‑antigen matrix is presented. The MAP system uses a three‑level lysine core with eight peptide termini, enabling a single solid‑phase synthesis of a ~10 kDa macromolecule bearing 2n peptide antigens. Six MAPs induced specific antibodies in rabbits and mice, five of which cross‑reacted with native proteins, and rabbit sera showed higher titers than keyhole limpet hemocyanin conjugates, demonstrating that MAPs provide a reproducible, carrier‑bound antigen platform suitable for vaccine development.

Abstract

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.