Design, synthesis and characterisation of mannosylated ovalbumin lipid core peptide self-adjuvanting vaccine delivery system.

Abstract

Peptide-based vaccine delivery can be hampered by rapid peptidase activity and poor inherent immunogenicity. The self-adjuvanting lipid core peptide system (LCP) has been shown to confer improved stability and immunogenicity on peptide epitopes of group A Streptococcus, Chlamydia, hookworm, and malaria pathogens. However, various diseases, including cancer, still require targeted delivery of their vaccine candidates. For this reason, we have selected two model peptides (ovalbumin CD4(+) and/or CD8(+) T cell epitopes), and incorporated two or four copies of either epitope into our LCP vaccine. Optimised glycosylation of ovalbumin peptides yielded 46 % when microwave-assisted double coupling with 2 eq of carbohydrate derivative, activated by N,N-diisopropylethylamine and (O-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, was performed. All ovalbumin peptides were successfully synthesised and purified in 11-55 % yields by Fmoc- or Boc-chemistry using solid-phase peptide synthesis. The mannosylated ovalbumin peptides were nontoxic to human erythrocytes in haemolytic assay (<2 % haemolysis) and showed increased (up to 20-fold) stability in plasma.

• Authors: Pavla Simerska, Zyta Maria Ziora, Vincent Fagan, Daryn Goodwin, Farrah Edrous, Istvan Toth
• Journal: Drug delivery and translational research (Drug Deliv Transl Res) Vol. 4 Issue 3 Pg. 246-55 (Jun 2014) ISSN: 2190-3948 [Electronic] United States
• PMID: 25786879 (Publication Type: Journal Article)