title: RrgB321, a fusion protein of the three variants of the pneumococcal pilus backbone RrgB, is protective in vivo and elicits opsonic antibodies.
abstract: Streptococcus pneumoniae pilus 1 is present in 30 to 50% of invasive disease-causing strains and is composed of three subunits: the adhesin RrgA, the major backbone subunit RrgB, and the minor ancillary protein RrgC. RrgB exists in three distinct genetic variants and, when used to immunize mice, induces an immune response specific for each variant. To generate an antigen able to protect against the infection caused by all pilus-positive S. pneumoniae strains, we engineered a fusion protein containing the three RrgB variants (RrgB321). RrgB321 elicited antibodies against proteins from organisms in the three clades and protected mice against challenge with piliated pneumococcal strains. RrgB321 antisera mediated complement-dependent opsonophagocytosis of piliated strains at levels comparable to those achieved with the PCV7 glycoconjugate vaccine. These results suggest that a vaccine composed of RrgB321 has the potential to cover 30% or more of all pneumococcal strains and support the inclusion of this fusion protein in a multicomponent vaccine against S. pneumoniae.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics s.r.l., Siena, Italy.
authors.forename: Carole
authors.initials: C
authors.lastname: Harfouche
authors.forename: Sara
authors.initials: S
authors.lastname: Filippini
authors.forename: Claudia
authors.initials: C
authors.lastname: Gianfaldoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggiero
authors.forename: Monica
authors.initials: M
authors.lastname: Moschioni
authors.forename: Silvia
authors.initials: S
authors.lastname: Maccari
authors.forename: Laura
authors.initials: L
authors.lastname: Pancotto
authors.forename: Letizia
authors.initials: L
authors.lastname: Arcidiacono
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.forename: Stefano
authors.initials: S
authors.lastname: Censini
authors.forename: Elena
authors.initials: E
authors.lastname: Mori
authors.forename: Marzia
authors.initials: M
authors.lastname: Giuliani
authors.forename: Claudia
authors.initials: C
authors.lastname: Facciotti
authors.forename: Elena
authors.initials: E
authors.lastname: Cartocci
authors.forename: Silvana
authors.initials: S
authors.lastname: Savino
authors.forename: Francesco
authors.initials: F
authors.lastname: Doro
authors.forename: Michele
authors.initials: M
authors.lastname: Pallaoro
authors.forename: Salvatore
authors.initials: S
authors.lastname: Nocadello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.forename: Mitch
authors.initials: M
authors.lastname: Haston
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.forename: Michèle A
authors.initials: MA
authors.lastname: Barocchi
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Vega
authors.initials: V
authors.lastname: Masignani
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000097:blood*; D010587:Phagocytosis / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D036781:Fimbriae Proteins; D003165:Complement System Proteins
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