title: Self-adjuvanting vaccine against group A streptococcus: application of fibrillized peptide and immunostimulatory lipid as adjuvant.
abstract: Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity. Recently, fibril-forming peptides such as Q11 and lipoamino acid-based carrier have been identified to induce substantial immune responses when covalently linked to peptide epitope. In this study, we have incorporated either Q11 or lipoamino acids to a peptide epitope (J14) derived from M protein of group A streptococcus to develop self-adjuvanting vaccines. J14, Q11 and lipoamino acids were also conjugated together in a single vaccine construct in an attempt to evaluate the synergy effect of combining multiple adjuvants. Physicochemical characterization demonstrated that the vaccine constructs folded differently and self-assembled into nanoparticles. Significantly, only vaccine constructs containing double copies of lipoamino acids (regardless in conjugation with Q11 or not) were capable to induce significant dendritic cells uptake and subsequent J14-specific antibody responses in non-sizes dependent manners. Q11 had minimal impact in enhancing the immunogenicity of J14 even when it was used in combination with lipoamino acids. These findings highlight the impact of lipoamino acids moiety as a promising immunostimulant carrier and its number of attachment to peptide epitope was found to have a profound effect on the vaccine immunogenicity.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia; Faculty of Pharmacy, National University of Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Fazren
authors.initials: F
authors.lastname: Azmi
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia.
authors.forename: Abdullah Al Hadi
authors.initials: AA
authors.lastname: Ahmad Fuaad
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia.
authors.forename: Ashwini Kumar
authors.initials: AK
authors.lastname: Giddam
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, St Lucia, Queensland 4072, Australia. Electronic address: i.toth@uq.edu.au.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002942:Circular Dichroism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D055666:Lipopeptides / Q000737:chemistry* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D013297:Streptococcus pyogenes / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D055666:Lipopeptides; D014614:Vaccines, Synthetic
keywords: Delivery; Fibril; Group A streptococcus; Lipopeptide; Peptide; Vaccine