title: Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus.
abstract: Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity. Nanoparticles were prepared by either encapsulating or coating lipopeptide-based vaccine candidate (LCP-1) on the surface of poly(lactic-co-glycolic acid) (PLGA). In vitro study showed that encapsulation of LCP-1 vaccine into nanoparticles improved uptake and maturations of antigen-presenting cells. The immunogenicity of lipopeptide incorporated PLGA-based nanoparticles was compared with peptides co-administered with mucosal adjuvant cholera toxin B in mice upon intranasal administration. Higher levels of J14-specific salivary mucosal IgA and systemic antibody IgG titres were observed for groups immunized with encapsulated LCP-1 compared to LCP-1 coated nanoparticles or free LCP-1. Systemic antibodies obtained from LCP-1 encapsulated PLGA NPs inhibited the growth of bacteria in six different GAS strains. Our results show that PLGA-based lipopeptide delivery is a promising approach for rational design of a simple, effective and patient friendly intranasal GAS vaccine resulting in mucosal IgA response.
authors.affiliation: The University of Queensland, School of Chemistry & Molecular Biosciences, St Lucia, QLD, 4072, Australia.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Marasini
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD, 4072, Australia; The University of Queensland, Dimantina Institute, Woolloongabba, QLD, 4102, Australia.
authors.forename: Zeinab G
authors.initials: ZG
authors.lastname: Khalil
authors.affiliation: The University of Queensland, School of Chemistry & Molecular Biosciences, St Lucia, QLD, 4072, Australia.
authors.forename: Ashwini Kumar
authors.initials: AK
authors.lastname: Giddam
authors.affiliation: The University of Queensland, School of Chemistry & Molecular Biosciences, St Lucia, QLD, 4072, Australia.
authors.forename: Khairunnisa Abdul
authors.initials: KA
authors.lastname: Ghaffar
authors.affiliation: The University of Queensland, School of Chemistry & Molecular Biosciences, St Lucia, QLD, 4072, Australia.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Hussein
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD, 4072, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
authors.affiliation: Griffith University, Institute for Glycomics, Gold Coast, QLD, 4222, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: Griffith University, Institute for Glycomics, Gold Coast, QLD, 4222, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.affiliation: The University of Queensland, School of Chemistry & Molecular Biosciences, St Lucia, QLD, 4072, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: The University of Queensland, School of Chemistry & Molecular Biosciences, St Lucia, QLD, 4072, Australia; The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD, 4072, Australia; The University of Queensland, School of Pharmacy, Woolloongabba, QLD, 4102, Australia. Electronic address: i.toth@uq.edu.au.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D002772:Cholera Toxin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage*; D055666:Lipopeptides / Q000008:administration & dosage*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D022541:Streptococcal Vaccines / Q000008:administration & dosage*; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D055666:Lipopeptides; D022541:Streptococcal Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002772:Cholera Toxin
keywords: Lipopeptides; Mucosal immunology; Nanoparticles; PLGA; Vaccine