Conjugation of capsular polysaccharide to α-haemolysin from Staphylococcus aureus as a glycoprotein antigen

Reynaud-Rondier, L

doi:10.1016/0378-1097(91)90066-j

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…Because capsular antigens comprise effective vaccines against other encapsulated bacterial pathogens, early efforts in S. aureus vaccine development focused on these components. Covalent coupling of CP5 and CP8 to protein carrier molecules significantly increases their immunogenicity and Tcell-dependent properties (31)(32)(33). CP5/CP8-based conjugate vaccines alone failed in clinical trials aimed at reducing bacteremia in hemodialysis patients (34,35).…”

Section: Discussionmentioning

confidence: 99%

Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis

et al. 2014

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cStaphylococcus aureus is an invasive bacterial pathogen, and antibiotic resistance has impeded adequate control of infections caused by this microbe. Moreover, efforts to prevent human infections with single-component S. aureus vaccines have failed. In this study, we evaluated the protective efficacy in rats of vaccines containing both S. aureus capsular polysaccharides (CPs) and proteins. The serotypes 5 CP (CP5) and 8 CP (CP8) were conjugated to tetanus toxoid and administered to rats alone or together with domain A of clumping factor A (ClfA) or genetically detoxified alpha-toxin (dHla). The vaccines were delivered according to a preventive or a therapeutic regimen, and their protective efficacy was evaluated in a rat model of osteomyelitis. Addition of dHla (but not ClfA) to the CP5 or CP8 vaccine induced reductions in bacterial load and bone morphological changes compared with immunization with either conjugate vaccine alone. Both the prophylactic and therapeutic regimens were protective. Immunization with dHla together with a pneumococcal conjugate vaccine used as a control did not reduce staphylococcal osteomyelitis. The emergence of unencapsulated or small-colony variants during infection was negligible and similar for all of the vaccine groups. In conclusion, addition of dHla to a CP5 or CP8 conjugate vaccine enhanced its efficacy against S. aureus osteomyelitis, indicating that the inclusion of multiple antigens will likely enhance the efficacy of vaccines against both chronic and acute forms of staphylococcal disease.

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Section: Discussionmentioning

confidence: 99%

Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis

et al. 2014

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“…Polysaccharide-protein conjugate vaccines elicit high levels of polysaccharide-specific antibodies, and antibody levels rise following booster doses of the vaccine. Several laboratories have synthesized conjugate vaccines consisting of S. aureus CP5 and CP8 covalently linked to protein (27,37,94). These conjugates are highly immunogenic in mice, cows, and humans, and they induce antibodies that opsonize serotype 5 and 8 S. aureus strains for phagocytosis (27,28).…”

Section: Protection Afforded By Cp5 and Cp8 Antigensmentioning

confidence: 99%

Staphylococcus aureusCapsular Polysaccharides

2004

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Serotype 5 and 8 capsular polysaccharides predominate among clinical isolates of Staphylococcus aureus. The results of experiments in animal models of infection have revealed that staphylococcal capsules are important in the pathogenesis of S. aureus infections. The capsule enhances staphylococcal virulence by impeding phagocytosis, resulting in bacterial persistence in the bloodstream of infected hosts. S. aureus capsules also promote abscess formation in rats. Although the capsule has been shown to modulate S. aureus adherence to endothelial surfaces in vitro, animal studies suggest that it also promotes bacterial colonization and persistence on mucosal surfaces. S. aureus capsular antigens are surface associated, limited in antigenic specificity, and highly conserved among clinical isolates. With the emergence of vancomycin-resistant S. aureus in the United States in 2002, new strategies are needed to combat staphylococcal infections. Purified serotype 5 and 8 capsular polysaccharides offer promise as target antigens for a vaccine to prevent staphylococcal infections, although the inclusion of other antigens is likely to be essential in the development of an effective S. aureus vaccine. The genetics and mechanisms of capsule biosynthesis are complex, and much work remains to enhance our understanding of capsule biosynthesis and its regulation

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“…Additional studies must determine whether capsular antibodies are protective in other models of staphylococcal infection. Recently, several laboratories have synthesized conjugate vaccines consisting of S. aureus capsular polysaccharide covalently linked to protein (13,18,32). Whether antibodies elicited by conjugate vaccines protect animals against staphylococcal infections remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to capsular polysaccharides are not protective against experimental Staphylococcus aureus endocarditis

Nemeth

Lee

1995

Infect Immun

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The protective efficacy of antibodies to the Staphylococcus aureus capsular polysaccharide was examined in a rat model of catheter-induced endocarditis. Capsular antibodies were induced either by active immunization with killed S. aureus or by passive immunization with hyperimmune rabbit antiserum to S. aureus. Control rats were injected with phosphate-buffered saline or passively immunized with normal rabbit serum or rabbit antiserum to a nonencapsulated strain. Animals with indwelling catheters were challenged intravenously with 5 ؋ 10 4 to 4 ؋ 10 6 CFU of the homologous S. aureus strain (capsular serotype 5 strain Reynolds or serotype 1 strain SA1 mucoid). Both immunized and control rats developed S. aureus endocarditis. The numbers of S. aureus cells recovered from the blood and aortic valve vegetations of immunized rats were similar to those of control rats, indicating that capsule-specific antibodies were not protective. To determine whether the presence of an indwelling catheter interfered with antibody-mediated protection against S. aureus endocarditis, catheters were removed 2 h after insertion in additional groups of rats. An inoculum of 10 8 CFU of strain Reynolds was needed to provoke endocarditis in rats catheterized for 2 h, compared with 5 ؋ 10 4 CFU for rats with indwelling catheters. Passively transferred capsular antibodies were not protective since both immunized and nonimmunized animals developed endocarditis, and quantitative cultures of blood and valvular vegetations revealed no differences between immunized and control animals. The findings of this study indicate that antibodies to the capsular polysaccharide are not protective in the rat model of experimental S. aureus endocarditis.

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Conjugation of capsular polysaccharide to α-haemolysin from Staphylococcus aureus as a glycoprotein antigen

Cited by 3 publications

References 11 publications

Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis

Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis

Staphylococcus aureusCapsular Polysaccharides

Antibodies to capsular polysaccharides are not protective against experimental Staphylococcus aureus endocarditis

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