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

Simerska, Pavla, Ziora, Zyta Maria, Fagan, Vincent, Goodwin, Daryn, Edrous, Farrah and Toth, Istvan (2013) Design, synthesis and characterisation of mannosylated ovalbumin lipid core peptide self-adjuvanting vaccine delivery system. Drug Delivery and Translational Research, Online First 3: 1-10. doi:10.1007/s13346-013-0173-8

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Simerska, Pavla
Ziora, Zyta Maria
Fagan, Vincent
Goodwin, Daryn
Edrous, Farrah
Toth, Istvan
Title Design, synthesis and characterisation of mannosylated ovalbumin lipid core peptide self-adjuvanting vaccine delivery system
Journal name Drug Delivery and Translational Research   Check publisher's open access policy
ISSN 2190-393X
2190-3948
ISBN 978-1-61779-150-5
Publication date 2013-09-18
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s13346-013-0173-8
Open Access Status Not yet assessed
Volume Online First
Issue 3
Start page 1
End page 10
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
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.
Formatted 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.
Keyword Vaccine development
Peptide synthesis
Ovalbumin
Glycosylation
In vitro assay
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP1092829
APP1026488
Institutional Status UQ
Additional Notes Published online: 18 September 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 2 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 03 Sep 2013, 01:29:28 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences