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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
- Source :
- Vaccine, Vaccine; Vol 29
- Publication Year :
- 2011
-
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.
- Subjects :
- Cross Protection
Phagocytosis
Heterologous
Microbiologia
Cross Reactions
Biology
medicine.disease_cause
Pneumococcal Infections
Virulence factor
Microbiology
Pneumococcal Vaccines
Mice
03 medical and health sciences
Bacterial Proteins
Sepsis
Streptococcus pneumoniae
medicine
Animals
Humans
030304 developmental biology
Vaccines, Synthetic
0303 health sciences
Vaccini
General Veterinary
General Immunology and Microbiology
030306 microbiology
Public Health, Environmental and Occupational Health
Antibodies, Bacterial
Virology
3. Good health
Infectious Diseases
IgG binding
Immunoglobulin G
Factor H
Humoral immunity
Mice, Inbred CBA
biology.protein
Molecular Medicine
Antibody
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Vaccine, Vaccine; Vol 29
- Accession number :
- edsair.doi.dedup.....36a158559c7067fafc80ce9e5a2719ea