title: Intranasal vaccination with SfbI or M protein-derived peptides conjugated to diphtheria toxoid confers protective immunity against a lethal challenge with Streptococcus pyogenes.
abstract: We investigated whether intranasal immunisation with diphtheria toxoid (DT) conjugated polypeptides encompassing T and B cell epitopes of the SfbI protein (FNBR) or a conformational-constrained B cell epitope of the M1 protein (J8) was able to confer protection against lethal mucosal challenge with a heterologous Streptococcus pyogenes strain. To this end, BALB/c mice were immunised with the conjugates. Strong antigen-specific antibody responses were observed in both serum and mucosal secretions. Vaccinated mice were challenged 10 days after the last boost by the intranasal route. Animals receiving FNBR-DT co-administered with either the cholera toxin B subunit (CTB) or the TLR 2/6 agonist MALP-2 were efficiently protected against the virulent S. pyogenes strain (90% and 70% survival, respectively), whereas those immunised with J8-DT plus either CTB or MALP-2 showed intermediate levels of protection (60% and 40%, respectively). The obtained results indicate that in our experimental animal model peptide-based conjugate vaccines represent a valid alternative to protect against streptococcal infection.
authors.affiliation: Department of Vaccinology, GBF-German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. ksc@gbf.de
authors.forename: Kai
authors.initials: K
authors.lastname: Schulze
authors.forename: Colleen
authors.initials: C
authors.lastname: Olive
authors.forename: Thomas
authors.initials: T
authors.lastname: Ebensen
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzmán
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000276:immunology*; D002772:Cholera Toxin; D004168:Diphtheria Toxoid; D005260:Female; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000737:chemistry; D044967:Serum / Q000737:chemistry; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control; D013297:Streptococcus pyogenes / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051216:Toll-Like Receptor 6 / Q000819:agonists; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004168:Diphtheria Toxoid; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D022223:Vaccines, Subunit; D002772:Cholera Toxin