Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates

Amy Chan; Waleed M Hussein; Khairunnisa Abdul Ghaffar; Nirmal Marasini; Ahmed Mostafa; Sharareh Eskandari; Michael R Batzloff; Michael F Good; Mariusz Skwarczynski; Istvan Toth

doi:10.1016/j.bmc.2016.03.063

Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates

Bioorg Med Chem. 2016 Jul 15;24(14):3095-101. doi: 10.1016/j.bmc.2016.03.063. Epub 2016 Apr 2.

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
² School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia; Faculty of Pharmacy, Helwan University, Ein Helwan, Helwan, Egypt.
³ Institute for Glycomics, Griffith University, Gold Coast 4215, Australia.
⁴ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia; School of Pharmacy, The University of Queensland, Brisbane 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia. Electronic address: i.toth@uq.edu.au.

PMID: 27246859
DOI: 10.1016/j.bmc.2016.03.063

Abstract

Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside a universal T-helper epitope (P25) in four LCP constructs of different spatial orientation or LAA lengths. Through structure-activity studies, it was discovered that while the alteration of the LCP orientation had a weaker effect on immunostimulation, increasing the LAA side chain length within the construct increased antibody responses in murine models. Furthermore, the mice immunised with the lead LCP construct were also able to maintain antibody activity throughout the course of five months. These findings highlight the importance of LAA moieties in the development of intranasal peptide vaccines and confirmed that its side chain length has an effect on the immunogenicity of the structure.

Keywords: Adjuvant; Copper-catalysed azide–alkyne cycloaddition; Group A Streptococcus; Lipopeptides; Peptide vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Bacterial Vaccines / chemistry*
Bacterial Vaccines / pharmacology*
Enzyme-Linked Immunosorbent Assay
Epitopes / chemistry
Lipids / chemistry*
Mice
Microscopy, Electron, Transmission
Peptides / chemistry*
Streptococcus pyogenes / immunology*
Structure-Activity Relationship

Substances

Bacterial Vaccines
Epitopes
Lipids
Peptides