title: Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice.
abstract: The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were studied. In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis. Unlike the disaccharide rabbit antisera, tri- and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci. All these rabbit antisera passively protected mice against a Pn 6B challenge. The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge. In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates. These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci. In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively.
authors.affiliation: Vaccines Section, Eijkman-Winkler Institute for Microbiology, Infectious Diseases, and Inflammation, Utrecht University Hospital, 3584 CX Utrecht, The Netherlands. JWO@GBF.de
authors.forename: W T
authors.initials: WT
authors.lastname: Jansen
authors.forename: S
authors.initials: S
authors.lastname: Hogenboom
authors.forename: M J
authors.initials: MJ
authors.lastname: Thijssen
authors.forename: J P
authors.initials: JP
authors.lastname: Kamerling
authors.forename: J F
authors.initials: JF
authors.lastname: Vliegenthart
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: H
authors.initials: H
authors.lastname: Snippe
authors.forename: A F
authors.initials: AF
authors.lastname: Verheul
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000276:immunology*; D010587:Phagocytosis; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000939:Epitopes; D007106:Immune Sera; D009844:Oligosaccharides; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin