Vaccine review: “Staphyloccocus aureus vaccines: Problems and prospects”

Jansen, Kathrin U.; Girgenti, Douglas; Scully, Ingrid L.; Anderson, Annaliesa S.

doi:10.1016/j.vaccine.2013.04.002

Cited by 127 publications

(104 citation statements)

References 116 publications

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“…This is especially critical in light of repeated experiences showing that vaccines and antibody-based approaches targeting S. aureus failed to show clinical efficacy despite supportive preclinical in vivo data generated in rodent models (mainly in mice) (21). Recent immune approaches increasingly employ cytolysins as vaccine antigens and as targets for human monoclonal antibody therapeutics (22,23).…”

Section: Discussionmentioning

confidence: 99%

Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin

Diep

Visram

et al. 2016

Antimicrob Agents Chemother

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b Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality. S. aureus strains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the leukocidins greatly contributes to the ambiguity regarding their role in S. aureus pathogenesis. We performed a comparative analysis of the leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbit S. aureus models. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-S. aureus therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin

Diep

Visram

et al. 2016

Antimicrob Agents Chemother

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“…50 While some Gram-negative organisms present clinical development challenges with regard to identifying appropriate patient population with high enough disease incidence to perform prophylactic vaccine clinical studies, for a pathogen such as E coli however, patient populations can be identified and promising vaccine approaches focusing on proteins, capsular polysaccharides and lipopolysaccharides (or O antigens) are being evaluated preclinically and clinically. 67-70 …”

Section: Vaccines In Early Stages Of Development With Potential To Rementioning

confidence: 99%

The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

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104

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The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR.

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“…none has successfully reached regulatory approval for S. aureus (24)(25)(26)(27). By combining the S. aureus-specific carbohydrate binding activity of selected autolysins and lysins with the Fc effector functions of human antibodies, we created three lysibodies specific to S. aureus.…”

Section: Significancementioning

confidence: 99%

Lysibodies are IgG Fc fusions with lysin binding domains targetingStaphylococcus aureuswall carbohydrates for effective phagocytosis

Raz

Serrano

Lawson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The cell wall of Gram-positive bacteria contains abundant surfaceexposed carbohydrate molecules that are highly conserved within and often across species. The potential therapeutic usefulness of high-affinity antibodies to cell wall carbohydrates is unquestioned, however obtaining such antibodies is challenging due to the poor overall immunogenicity of these bacterial targets. Autolysins and phage lysins are peptidoglycan hydrolases, enzymes that have evolved over a billion years to degrade bacterial cell wall. Such wall hydrolases are modular enzymes, composed of discrete domains for high-affinity binding to cell wall carbohydrates and cleavage activity. In this study, we demonstrate that binding domains from autolysins and lysins can be fused to the Fc region of human IgG, creating a fully functional homodimer (or "lysibody") with high-affinity binding and specificity for carbohydrate determinants on the bacterial surface. Furthermore, we demonstrate that this process is reproducible with three different binding domains specific to methicillin-resistant Staphylococcus aureus (MRSA). Cell-bound lysibodies induced the fixation of complement on the bacterial surface, promoted phagocytosis by macrophages and neutrophils, and protected mice from MRSA infection in two model systems. The lysibody approach could be used to target a range of difficult-to-treat pathogenic bacteria, given that cell wall hydrolases are ubiquitous in nature.immunotherapy | antibody | vaccine | monoclonal | peptidoglycan hydrolase

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Vaccine review: “Staphyloccocus aureus vaccines: Problems and prospects”

Cited by 127 publications

References 116 publications

Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin

Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin

The role of vaccines in fighting antimicrobial resistance (AMR)

Lysibodies are IgG Fc fusions with lysin binding domains targetingStaphylococcus aureuswall carbohydrates for effective phagocytosis

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