Effect of immunization with highly purified Panton-Valentine leucocidin and delta-toxin on staphylococcal mastitis in rabbits

Adlam, C.; Ward, P.D.; Turner, W.

doi:10.1016/0021-9975(80)90063-8

Cited by 24 publications

(24 citation statements)

References 15 publications

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“…Alpha toxoid was first suggested as a vaccine component in 1977, when it was shown to prevent the lethal gangrenous form of S. aureus mastitis in rabbits (45). Subsequently, a number of S. aureus vaccines composed of inactivated toxins or their subunits have been evaluated preclinically, and the results of these studies were reviewed recently (20,26).…”

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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“…One study, which immunized rabbits with PVL in order to prevent the pathological outcomes of mastitis, showed no efficacy (325). In contrast, another study suggested that the administration of intravenous immunoglobulin (IVIG) might have potential therapeutic value, as it is likely to contain a number of antitoxin antibodies.…”

Section: Targeting Of Leucocidins As a Therapeutic Modalitymentioning

confidence: 99%

The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus

Alonzo

Torres

2014

Microbiol Mol Biol Rev

236

290

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SUMMARY The ability to produce water-soluble proteins with the capacity to oligomerize and form pores within cellular lipid bilayers is a trait conserved among nearly all forms of life, including humans, single-celled eukaryotes, and numerous bacterial species. In bacteria, some of the most notable pore-forming molecules are protein toxins that interact with mammalian cell membranes to promote lysis, deliver effectors, and modulate cellular homeostasis. Of the bacterial species capable of producing pore-forming toxic molecules, the Gram-positive pathogen Staphylococcus aureus is one of the most notorious. S. aureus can produce seven different pore-forming protein toxins, all of which are believed to play a unique role in promoting the ability of the organism to cause disease in humans and other mammals. The most diverse of these pore-forming toxins, in terms of both functional activity and global representation within S. aureus clinical isolates, are the bicomponent leucocidins. From the first description of their activity on host immune cells over 100 years ago to the detailed investigations of their biochemical function today, the leucocidins remain at the forefront of S. aureus pathogenesis research initiatives. Study of their mode of action is of immediate interest in the realm of therapeutic agent design as well as for studies of bacterial pathogenesis. This review provides an updated perspective on our understanding of the S. aureus leucocidins and their function, specificity, and potential as therapeutic targets.

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“…Antibodies raised to alpha toxin detoxified with formaldehyde have been shown to protect monkeys against the toxic and lethal action of purified alpha toxin [11]. However, animals immunized with alpha toxoid and challenged with live bacteria are not generally protected from infection with alpha toxin-producing strains of S. aureus, although the clinical severity of their disease may be less than that in nonimmunized controls [2,[12][13][14]. Menzies and Kernodle [15] constructed a nontoxic alpha toxin mutant by replacing a histidine with a leucine at amino acid 35 (H35L toxin).…”

Section: Alpha Toxoidmentioning

confidence: 98%

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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Effect of immunization with highly purified Panton-Valentine leucocidin and delta-toxin on staphylococcal mastitis in rabbits

Cited by 24 publications

References 15 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

The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus

Development of antistaphylococcal vaccines

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