title: The factor H-binding fragment of PspC as a vaccine antigen for the induction of protective humoral immunity against experimental pneumococcal sepsis.
abstract: Pneumococcal surface protein C (PspC) is a major virulence factor of Streptococcus pneumoniae and interferes with complement activity by binding complement factor H (fH). In this study, protection against experimental sepsis caused by pneumococci carrying different PspC variants was evaluated by immunisation with the fH-binding fragment of PspC. The mechanisms of protection mediated by antibodies to PspC were also studied. Mice were immunised with a PspC fragment (PspC(39-261)) from the type 3 strain HB565 and infected intravenously with either strain HB565 (homologous challenge), or strains D39 and TIGR4 (heterologous challenge). Immunisation with PspC(39-261) elicited high titers (>300,000) of PspC-specific serum IgG and conferred protection from challenge with HB565. In contrast, cross-protection was either limited or absent in vaccinated animals infected with D39 and TIGR4, respectively. To correlate protection with reactivity and function of PspC antibodies, pooled sera from vaccinated mice were tested in IgG binding and complement deposition experiments. IgG antibodies efficiently bound to HB565, while binding was lower with D39 and absent with TIGR4. In the presence of mouse post-immune sera, C3 deposition was increased onto HB565, while no effect was observed with D39 and TIGR4. Antibody cross-reactivity and complement deposition progressively declined with reduced amino acid identity between PspC variants. Antibodies to PspC were also found to interfere with fH binding to HB565. Finally, in vitro and ex vivo phagocytosis assays demonstrated that PspC-specific antibodies promoted opsonophagocytic killing of bacteria.
authors.affiliation: Department of Biotechnology, University of Siena, Italy. susanna.ricci@unisi.it
authors.forename: Susanna
authors.initials: S
authors.lastname: Ricci
authors.forename: Robert
authors.initials: R
authors.lastname: Janulczyk
authors.forename: Alice
authors.initials: A
authors.lastname: Gerlini
authors.forename: Velia
authors.initials: V
authors.lastname: Braione
authors.forename: Leonarda
authors.initials: L
authors.lastname: Colomba
authors.forename: Francesco
authors.initials: F
authors.lastname: Iannelli
authors.forename: Damiana
authors.initials: D
authors.lastname: Chiavolini
authors.forename: Marco Rinaldo
authors.initials: MR
authors.lastname: Oggioni
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; C110344:SpsA protein, Streptococcus pneumoniae; D014614:Vaccines, Synthetic