title: Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate.
abstract: Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Kabanova
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
authors.forename: Francesco
authors.initials: F
authors.lastname: Berti
authors.forename: Maria R
authors.initials: MR
authors.lastname: Romano
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.forename: Emiliano
authors.initials: E
authors.lastname: Chiarot
authors.forename: Daniela
authors.initials: D
authors.lastname: Proietti
authors.forename: Erwin
authors.initials: E
authors.lastname: Swennen
authors.forename: Emilia
authors.initials: E
authors.lastname: Cappelletti
authors.forename: Paola
authors.initials: P
authors.lastname: Fontani
authors.forename: Daniele
authors.initials: D
authors.lastname: Casini
authors.forename: Roberto
authors.initials: R
authors.lastname: Adamo
authors.forename: Vittoria
authors.initials: V
authors.lastname: Pinto
authors.forename: David
authors.initials: D
authors.lastname: Skibinski
authors.forename: Sabrina
authors.initials: S
authors.lastname: Capo
authors.forename: Giada
authors.initials: G
authors.lastname: Buffi
authors.forename: Marilena
authors.initials: M
authors.lastname: Gallotta
authors.forename: William J
authors.initials: WJ
authors.lastname: Christ
authors.forename: A Stewart
authors.initials: AS
authors.lastname: Campbell
authors.forename: John
authors.initials: J
authors.lastname: Pena
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Costantino
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000276:immunology*; D010587:Phagocytosis; D011817:Rabbits; D044967:Serum / Q000276:immunology; D022541:Streptococcal Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D009844:Oligosaccharides; D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic