title: Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates.
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.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Chan
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia; Faculty of Pharmacy, Helwan University, Ein Helwan, Helwan, Egypt.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Hussein
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Khairunnisa Abdul
authors.initials: KA
authors.lastname: Ghaffar
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Marasini
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia; Faculty of Pharmacy, Helwan University, Ein Helwan, Helwan, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mostafa
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Eskandari
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast 4215, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast 4215, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: 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.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D001428:Bacterial Vaccines; D000939:Epitopes; D008055:Lipids; D010455:Peptides
keywords: Adjuvant; Copper-catalysed azide–alkyne cycloaddition; Group A Streptococcus; Lipopeptides; Peptide vaccine