Vaccination against Staphylococcus aureus mastitis: immunological response of mice vaccinated with fibronectin-binding protein (FnBP-A) to challenge with S. aureus

Mamo, Wubshet; Jönsson, Per; Flock, Jan‐Ingmar; Lindberg, Martin; Müller, Hans‐Peter; Wadström, Torkel; Nelson, Lennart

doi:10.1016/0264-410x(94)90333-6

Cited by 75 publications

(38 citation statements)

References 22 publications

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“…Because of the multiplicity of S. aureus virulence factors, it is rather unlikely that immunization with a single protein would confer absolute protection. Previously published data impressively demonstrate this notion (21,32,33,37,50).…”

Section: Discussionmentioning

confidence: 67%

Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates againstStaphylococcus aureus

et al. 2009

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Staphylococcus aureus is an important human pathogen with increasing clinical impact due to the extensive spread of antibiotic-resistant strains. Therefore, development of a protective polyvalent vaccine is of great clinical interest. We employed an intravenous immunoglobulin (IVIG) preparation as a source of antibodies directed against anchorless S. aureus surface proteins for identification of novel vaccine candidates. In order to identify such proteins, subtractive proteome analysis (SUPRA) of S. aureus anchorless cell wall proteins was performed. Proteins reacting with IVIG but not with IVIG depleted of S. aureus-specific opsonizing antibodies were considered vaccine candidates. Nearly 40 proteins were identified by this preselection method using matrix-assisted laser desorption ionization-time of flight analysis. Three of these candidate proteins, enolase (Eno), oxoacyl reductase (Oxo), and hypothetical protein hp2160, were expressed as glutathione S-transferase fusion proteins, purified, and used for enrichment of corresponding immunoglobulin Gs from IVIG by affinity chromatography. Use of affinity-purified anti-Eno, anti-Oxo, and anti-hp2160 antibodies resulted in opsonization, phagocytosis, and killing of S. aureus by human neutrophils. High specific antibody titers were detected in mice immunized with recombinant antigens. In mice challenged with bioluminescent S. aureus, reduced staphylococcal spread was measured by in vivo imaging. The recovery of S. aureus CFU from organs of immunized mice was diminished 10-to 100-fold. Finally, mice immunized with hp2160 displayed statistically significant higher survival rates after lethal challenge with clinically relevant S. aureus strains. Taken together, our data suggest that anchorless cell wall proteins might be promising vaccine candidates and that SUPRA is a valuable tool for their identification.

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Section: Discussionmentioning

confidence: 67%

Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates againstStaphylococcus aureus

et al. 2009

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“…A number of studies have shown bacterial binding to ECM components and documented its role in infection. Thus, S. aureus binding to fibronectin via FnBP-A (fibronectin binding protein) or to collagen via CNBP (collagen binding protein) has been shown to play a role in animal models of infection (20,22,24,26). In Yersinia species, mutations of the YadA surface protein causing loss of collagen binding resulted in a loss of virulence in mice (33).…”

Section: Discussionmentioning

confidence: 99%

Binding of Clostridium difficile Surface Layer Proteins to Gastrointestinal Tissues

et al. 2002

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Clostridium difficile is the etiological agent of antibiotic-associated diarrhea, a potentially serious condition frequently affecting elderly hospitalized patients. While tissue damage is primarily induced by two toxins, the mechanism of gut colonization, and particularly the role of bacterial adherence to the mucosa, remains to be clarified. Previous studies have shown binding of C. difficile whole cells to cultured cell lines and suggested the existence of multiple adhesins, only one of which has been molecularly characterized. In this paper, we have investigated tissue binding of C. difficile surface layer proteins (SLPs), which are the predominant outer surface components and are encoded by the slpA gene. The adherence of C. difficile to HEp-2 cells was studied by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis, which showed that antibodies to the high-molecular-weight (MW) SLP inhibited adherence. Immunohistochemical analysis of human gastrointestinal tissue sections revealed strong binding both to the surface epithelium lining the digestive cavities and to the subjacent lamina propria, while glands were negative. A similar pattern was observed in the mouse. By using purified recombinant SLPs, we show that binding is largely mediated by the high-MW SLP. By Western blotting analysis, we have identified two potential ligands of the C. difficile SLPs, one of which may be specific to the gut. By using purified extracellular matrix components immobilized on nitrocellulose, we also show SLP binding to collagen I, thrombospondin, and vitronectin, but not to collagen IV, fibronectin, or laminin. These results raise the possibility that the SLPs play a role both in the initial colonization of the gut by C. difficile and in the subsequent inflammatory reaction.

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“…As part of the effort to develop a multicomponent vaccine against S. aureus, several vaccine candidates are currently being evaluated in animal models of staphylococcal infection or in human clinical trials. The most promising candidates to date include adhesins (fibronectinbinding protein, collagen-binding protein, and fibrinogenbinding protein [clumping factor]), a nontoxic alpha toxin mutant, and capsular polysaccharides type 5 and 8. did control mice (immunized with adjuvant alone), and fewer bacteria were recovered from the mammary glands of vaccinees than from those of control mice [2].…”

Section: Fibronectin-binding Proteinsmentioning

confidence: 97%

Development of antistaphylococcal vaccines

Lee

2001

Curr Infect Dis Rep

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Staphylococcus aureus is frequently isolated from both hospital-acquired and community-acquired infections, and the emergence of antibiotic resistance among clinical isolates has made treatment of staphylococcal infections difficult. This scenario has sparked renewed interest in the development of a vaccine for individuals at high risk for staphylococcal infections. As part of the effort to develop a multicomponent vaccine against S. aureus, several vaccine candidates are currently being evaluated in animal models of staphylococcal infection or in human clinical trials. The most promising candidates to date include adhesins (fibronectin-binding protein, collagen-binding protein, and fibrinogen-binding protein ), a nontoxic alpha toxin mutant, and capsular polysaccharides type 5 and 8.

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Vaccination against Staphylococcus aureus mastitis: immunological response of mice vaccinated with fibronectin-binding protein (FnBP-A) to challenge with S. aureus

Cited by 75 publications

References 22 publications

Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates againstStaphylococcus aureus

Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates againstStaphylococcus aureus

Binding of Clostridium difficile Surface Layer Proteins to Gastrointestinal Tissues

Development of antistaphylococcal vaccines

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