title: Novel platform technology for modular mucosal vaccine that protects against streptococcus.
abstract: The upper respiratory tract (URT) is the major entry site for human pathogens and strategies to activate this network could lead to new vaccines capable of preventing infection with many pathogens. Group A streptococcus (GAS) infections, causing rheumatic fever, rheumatic heart disease, and invasive disease, are responsible for substantial morbidity and mortality. We describe an innovative vaccine strategy to induce mucosal antibodies of significant magnitude against peptide antigens of GAS using a novel biocompatible liposomal platform technology. The approach is to encapsulate free diphtheria toxoid (DT), a standard vaccine antigen, within liposomes as a source of helper T-cell stimulation while lipidated peptide targets for B-cells are separately displayed on the liposome surface. As DT is not physically conjugated to the peptide, it is possible to develop modular epitopic constructs that simultaneously activate IgA-producing B-cells of different and complementary specificity and function that together neutralize distinct virulence factors. An inflammatory cellular immune response is also induced. The immune response provides profound protection against streptococcal infection in the URT. The study describes a new vaccine platform for humoral and cellular immunity applicable to the development of vaccines against multiple mucosal pathogens.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Mehfuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ozberk
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Langshaw
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Virginia
authors.initials: V
authors.lastname: McPhun
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Powell
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Phillips
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Mei Fong
authors.initials: MF
authors.lastname: Ho
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Ainslie
authors.initials: A
authors.lastname: Calcutt
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, QLD 4072, Australia.|The University of Queensland, School of Pharmacy, Woolloongabba, QLD 4102, Australia.|Institute for Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.affiliation: QIMR Berghofer Medical Research Institute, QIMR Berghofer Centre for Immunotherapy and Vaccine Development, Brisbane QLD 4029, Australia.|Bone Marrow Transplant Unit, Royal Brisbane Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Manisha
authors.initials: M
authors.lastname: Pandey
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial / Q000276:immunology; D049109:Cell Proliferation; D000939:Epitopes / Q000737:chemistry; D007107:Immune System; D007249:Inflammation; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D010455:Peptides / Q000737:chemistry; D013154:Spleen / Q000166:cytology; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D008081:Liposomes; D010455:Peptides; D022541:Streptococcal Vaccines; D037521:Virulence Factors