title: A semisynthetic carbohydrate-lipid vaccine that protects against S. pneumoniae in mice.
abstract: Severe forms of pneumococcal meningitis, bacteraemia and pneumonia result in more than 1 million deaths each year despite the widespread introduction of carbohydrate-protein conjugate vaccines against Streptococcus pneumoniae. Here we describe a new and highly efficient antipneumococcal vaccine design based on synthetic conjugation of S. pneumoniae capsule polysaccharides to the potent lipid antigen α-galactosylceramide, which stimulates invariant natural killer T (iNKT) cells when presented by the nonpolymorphic antigen-presenting molecule CD1d. Mice injected with the new lipid-carbohydrate conjugate vaccine produced high-affinity IgG antibodies specific for pneumococcal polysaccharides. Vaccination stimulated germinal center formation; accumulation of iNKT cells with a T follicular helper cell phenotype; and increased frequency of carbohydrate-specific, long-lived memory B cells and plasmablasts. This new lipid-carbohydrate vaccination strategy induced potent antipolysaccharide immunity that protected against pneumococcal disease in mice and may also prove effective for the design of carbohydrate-based vaccines against other major bacterial pathogens.
authors.affiliation: Experimental Immunology Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Cavallari
authors.affiliation: Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Stallforth
authors.affiliation: Experimental Immunology Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
authors.forename: Artem
authors.initials: A
authors.lastname: Kalinichenko
authors.affiliation: Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Dominea C K
authors.initials: DC
authors.lastname: Rathwell
authors.affiliation: SAW Instruments, Bonn, Germany.
authors.forename: Thomas M A
authors.initials: TM
authors.lastname: Gronewold
authors.affiliation: Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Adibekian
authors.affiliation: 1] Experimental Immunology Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland. [2] SIgN (Singapore Immunology Network), A*STAR (Agency for Science, Technology and Research) Biopolis, Singapore.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.affiliation: Infection Biology, Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
authors.affiliation: Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.affiliation: 1] Experimental Immunology Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland. [2] SIgN (Singapore Immunology Network), A*STAR (Agency for Science, Technology and Research) Biopolis, Singapore.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002241:Carbohydrates / Q000008:administration & dosage / Q000737:chemistry*; D002460:Cell Line; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D007116:Immunization, Passive; D007156:Immunologic Memory / Q000276:immunology; D007700:Kinetics; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D055610:Antigens, CD1d; D002241:Carbohydrates; D008055:Lipids; D022242:Pneumococcal Vaccines; D014614:Vaccines, Synthetic