Safety, tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised, placebo-controlled phase 1/2 study

Frenck, Robert W.; Creech, C. Buddy; Sheldon, Eric; Seiden, David; Kankam, Martin; Baber, James; Zito, Edward T.; Hubler, Robin; Eiden, Joseph; Severs, Joseph; Sebastian, Shite; Nanra, Jasdeep S.; Jansen, Kathrin U.; Gruber, William C.; Anderson, Annaliesa S.; Girgenti, Douglas

doi:10.1016/j.vaccine.2016.11.010

Cited by 58 publications

(44 citation statements)

References 29 publications

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“…52 , 53 SA4Ag was shown to be safe, well tolerated in early stage clinical trials, and induced high levels of bacterial killing antibodies in healthy adults, leading to a fast-track designation by the U.S. FDA. 54 In addition, a separate 4 component S. aureus vaccine (4C-Staph) formulated with a TLR7-dependent adjuvant is under development. 55 …”

Section: Vaccines In Late Stage Development With Potential To Reduce Amrmentioning

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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Section: Vaccines In Late Stage Development With Potential To Reduce Amrmentioning

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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“…For example, multiple virulence factors target the complement pathway and immunoglobulin recognition to inhibit neutrophil phagocytosis and neutralizing one of these virulence factors is not likely to have a significant effect in vivo . Thus, vaccine approaches that simultaneously target multiple S. aureus virulence factors are needed and encouragingly some are in the pipeline (Torre et al, 2015; Frenck et al, 2016). …”

Section: Potential Of Therapeutics To Augment Neutrophil Function Agamentioning

confidence: 99%

Epic Immune Battles of History: Neutrophils vs. Staphylococcus aureus

Guerra

Borgogna

Patel

et al. 2017

Front. Cell. Infect. Microbiol.

124

111

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Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages. Staphylococcus aureus (S. aureus) is a prevalent Gram-positive bacterium that is a common commensal and causes a wide range of diseases from skin infections to endocarditis. Since its discovery, S. aureus has been a formidable neutrophil foe that has challenged the efficacy of this professional assassin. Indeed, proper clearance of S. aureus by neutrophils is essential to positive infection outcome, and S. aureus has developed mechanisms to evade neutrophil killing. Herein, we will review mechanisms used by S. aureus to modulate and evade neutrophil bactericidal mechanisms including priming, activation, chemotaxis, production of reactive oxygen species, and resolution of infection. We will also highlight how S. aureus uses sensory/regulatory systems to tailor production of virulence factors specifically to the triggering signal, e.g., neutrophils and defensins. To conclude, we will provide an overview of therapeutic approaches that may potentially enhance neutrophil antimicrobial functions.

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“…Vaccines are promising alternatives to antibiotics; however, antistaphylococcal vaccine development has not yet been successful in humans. Seven investigational S. aureus vaccines are currently undergoing development ( Table ). In this review, focus is placed on two of the seven investigational S. aureus vaccines that have reached advanced clinical trials (developed by GSK and Pfizer).…”

Section: Approaches To Developing Vaccines To Prevent Surgical‐site Imentioning

confidence: 99%

“…Seven investigational S. aureus vaccines are currently undergoing development ( Table ). In this review, focus is placed on two of the seven investigational S. aureus vaccines that have reached advanced clinical trials (developed by GSK and Pfizer). Two investigational S. aureus vaccines (developed by Merck and Nabi) that underwent unsuccessful efficacy testing in the past two decades, and are no longer undergoing development, are also reviewed.…”

Section: Approaches To Developing Vaccines To Prevent Surgical‐site Imentioning

confidence: 99%

Vaccine development to preventStaphylococcus aureussurgical-site infections

Mohamed

Wang

Huec³

et al. 2017

British Journal of Surgery

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Background: Staphylococcus aureus surgical-site infections (SSIs) are a major cause of poor health outcomes, including mortality, across surgical specialties. Despite current advances as a result of preventive interventions, the disease burden of S. aureus SSI remains high, and increasing antibiotic resistance continues to be a concern. Prophylactic S. aureus vaccines may represent an opportunity to prevent SSI.Methods: A review of SSI pathophysiology was undertaken in the context of evaluating new approaches to developing a prophylactic vaccine to prevent S. aureus SSI.Results: A prophylactic vaccine ideally would provide protective immunity at the time of the surgical incision to prevent initiation and progression of infection. Although the pathogenicity of S. aureus is attributed to many virulence factors, previous attempts to develop S. aureus vaccines targeted only a single virulence mechanism. The field has now moved towards multiple-antigen vaccine strategies, and promising results have been observed in early-phase clinical studies that supported the recent initiation of an efficacy trial to prevent SSI. Conclusion:There is an unmet medical need for novel S. aureus SSI prevention measures. Advances in understanding of S. aureus SSI pathophysiology could lead to the development of effective and safe prophylactic multiple-antigen vaccines to prevent S. aureus SSI.

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Safety, tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised, placebo-controlled phase 1/2 study

Abstract: NCT01364571.

Cited by 58 publications

References 29 publications

The role of vaccines in fighting antimicrobial resistance (AMR)

The role of vaccines in fighting antimicrobial resistance (AMR)

Epic Immune Battles of History: Neutrophils vs. Staphylococcus aureus

Vaccine development to preventStaphylococcus aureussurgical-site infections

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