title: Peptide mimics of two pneumococcal capsular polysaccharide serotypes (6B and 9V) protect mice from a lethal challenge with Streptococcus pneumoniae.
abstract: Anti-polysaccharide immunity is a key facet of protection against several bacterial pathogens. Problems exist with current polysaccharide vaccines and alternative strategies that deliver a protective response are needed. We have identified immunological peptide mimics of type 6B and 9V pneumococcal capsular polysaccharides that could be used as vaccine antigens. Peptides mimicking antigenic properties of serotype 6B capsular polysaccharide were obtained from a phage-displayed peptide library expressing dodecameric peptides, using a human monoclonal antibody (Db3G9). A murine monoclonal antibody (206, F-5) against the serotype 9V capsular polysaccharide identified three peptide mimotopes from the dodecameric peptide library and one from a random pentadecameric peptide library. In ELISA, binding of 206, F-5 and Db3G9 to phage displaying the selected mimotopes was significantly inhibited by type-specific pneumococcal polysaccharide. Peptides were conjugated to keyhole limpet haemocyanin and were used to immunise mice. Two peptides, MP13 and MP7, induced specific anti-6B and 9V polysaccharide antibodies, respectively. Mice immunised with MP7-keyhole limpet hemocyanin or MP13-keyhole limpet hemocyanin conjugate were significantly and specifically protected against a lethal challenge with pneumococci of the appropriate serotype. This study provides strong in vivo evidence that peptide mimics are alternatives to polysaccharide vaccines.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Smith
authors.forename: Carla
authors.initials: C
authors.lastname: Lo Passo
authors.forename: Angela
authors.initials: A
authors.lastname: Scuderi
authors.forename: Jan
authors.initials: J
authors.lastname: Kolberg
authors.forename: Helen
authors.initials: H
authors.lastname: Baxendale
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.forename: Marco R
authors.initials: MR
authors.lastname: Oggioni
authors.forename: Franco
authors.initials: F
authors.lastname: Felici
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053208:Kaplan-Meier Estimate; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D019151:Peptide Library; D010455:Peptides; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial