title: Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus.
abstract: Group A streptococcus (GAS), an exclusively human pathogen, causes a wide range of diseases ranging from trivial to life threatening. Treatment of infection is often ineffective following entry of bacteria into the bloodstream. To date, there is no vaccine available against GAS. In this study, cationic liposomes encapsulating lipopeptide-based vaccine candidates against GAS have been employed for intranasal vaccine delivery. Cationic liposomes were prepared with dimethyldioctadecylammonium bromide (DDAB) using the film hydration method. Female Swiss mice were immunized intranasally with the liposomes. In contrast to unmodified peptides, lipopeptides entrapped by liposomes induced both mucosal and systemic immunity, IgA and IgG (IgG1 and IgG2a) production in mice, respectively. High levels of antibody (IgA and IgG) titres were detected even five months post immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines.
  
  
  
  Group A streptococcus, causing rheumatic heart diseases, kills approximately half a million people annually. There is no vaccine available against the infection. Mucosal immunity is vital in ensuring an individual is protected as this gram positive bacteria initially colonizes at the throat. Herein, we demonstrated that lipopeptides entrapped by liposomes induced both mucosal and systemic immunity. High levels of antibody (IgA and IgG) titres were detected even five months post immunization and lead vaccine candidate was able to induce humoral immune responses even after single immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines.
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia.
authors.forename: Khairunnisa Abdul
authors.initials: KA
authors.lastname: Ghaffar
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Marasini
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia.
authors.forename: Ashwini Kumar
authors.initials: AK
authors.lastname: Giddam
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: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia; The University of Queensland, School of Pharmacy, Brisbane, QLD 4072, Australia; The University of Queensland, Institute for Molecular Biosciences, St Lucia, QLD 4072, Australia. Electronic address: i.toth@uq.edu.au.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D004705:Endocytosis; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D055666:Lipopeptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D008081:Liposomes; D051379:Mice; D022541:Streptococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D055666:Lipopeptides; D008081:Liposomes; D022541:Streptococcal Vaccines
keywords: Cationic liposomes; Group A Streptococcus; Intranasal immunization; Peptide vaccine