title: Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein/SfbI lipid core peptide vaccine formulation.
abstract: We investigated the efficacy of a synthetic Streptococcus pyogenes vaccine targeting two virulence factors using the Lipid Core Peptide (LCP) delivery system. BALB/c mice were immunised intranasally with LCPs containing peptides encompassing T-cell and B-cell epitopes of the conserved C-repeat region of the M protein (J8) or the fibronectin-binding repeats region (FNBR) of SfbI, or a combination formulation containing peptides representing both antigens. LCPs were co-administered with the TLR2/6 agonist MALP-2 as mucosal adjuvant. Humoral and cellular immune responses stimulated at systemic and mucosal levels were strongest in mice immunised with the dual antigen formulation. Mice were completely protected following a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain, whereas there was 70% and 90% survival in mice immunised with LCP-J8 and LCP-FNBR, respectively. This is the first report demonstrating the elicitation of better protective immunity by a dual antigen component S. pyogenes vaccine.
authors.affiliation: Cooperative Research Centre for Vaccine Technology, Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia. Colleen.OliveO@qimir.edu.au
authors.forename: C
authors.initials: C
authors.lastname: Olive
authors.forename: K
authors.initials: K
authors.lastname: Schulze
authors.forename: H Kuo
authors.initials: HK
authors.lastname: Sun
authors.forename: T
authors.initials: T
authors.lastname: Ebensen
authors.forename: A
authors.initials: A
authors.lastname: Horváth
authors.forename: I
authors.initials: I
authors.lastname: Toth
authors.forename: C A
authors.initials: CA
authors.lastname: Guzman
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D055666:Lipopeptides; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D055666:Lipopeptides; D009842:Oligopeptides; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C078635:fibronectin-binding proteins, bacterial; C014689:streptococcal M protein; C106335:macrophage stimulatory lipopeptide 2