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The factor H-binding fragment of PspC as a vaccine antigen for the induction of protective humoral immunity against experimental pneumococcal sepsis

Ricci, Susanna; Janulczyk, Robert LU ; Gerlini, Alice; Braione, Velia; Colomba, Leonarda; Iannelli, Francesco; Chiavolini, Damiana; Oggioni, Marco Rinaldo; Björck, Lars LU and Pozzi, Gianni (2011) In Vaccine 29(46). p.8241-8249
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... (More)
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 039 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 binding to HB565. Finally, in vitro and ex vivo phagocytosis assays demonstrated that PspC-specific antibodies promoted opsonophagocytic killing of bacteria. (C) 2011 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Streptococcus pneumoniae, PspC, Protection, Complement factor H, C3, deposition, Opsonophagocytosis
in
Vaccine
volume
29
issue
46
pages
8241 - 8249
publisher
Elsevier
external identifiers
  • wos:000296988500011
  • scopus:80053999318
ISSN
1873-2518
DOI
10.1016/j.vaccine.2011.08.119
language
English
LU publication?
yes
id
c545d2e2-b2b4-4acd-956c-cdfd3c621f00 (old id 2270396)
date added to LUP
2012-01-02 09:46:59
date last changed
2017-02-26 03:04:12
@article{c545d2e2-b2b4-4acd-956c-cdfd3c621f00,
  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 039 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 binding to HB565. Finally, in vitro and ex vivo phagocytosis assays demonstrated that PspC-specific antibodies promoted opsonophagocytic killing of bacteria. (C) 2011 Elsevier Ltd. All rights reserved.},
  author       = {Ricci, Susanna and Janulczyk, Robert and Gerlini, Alice and Braione, Velia and Colomba, Leonarda and Iannelli, Francesco and Chiavolini, Damiana and Oggioni, Marco Rinaldo and Björck, Lars and Pozzi, Gianni},
  issn         = {1873-2518},
  keyword      = {Streptococcus pneumoniae,PspC,Protection,Complement factor H,C3,deposition,Opsonophagocytosis},
  language     = {eng},
  number       = {46},
  pages        = {8241--8249},
  publisher    = {Elsevier},
  series       = {Vaccine},
  title        = {The factor H-binding fragment of PspC as a vaccine antigen for the induction of protective humoral immunity against experimental pneumococcal sepsis},
  url          = {http://dx.doi.org/10.1016/j.vaccine.2011.08.119},
  volume       = {29},
  year         = {2011},
}