Towards the immune proteome of Staphylococcus aureus – The anti-S. aureus antibody response

Holtfreter, Silva; Kolata, Julia; Bröker, Barbara M.

doi:10.1016/j.ijmm.2009.10.002

Cited by 98 publications

(105 citation statements)

References 149 publications

(193 reference statements)

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“…Part of the challenge in measuring the host response is the diversity and abundance of candidate antigens, noted above. Some investigators used whole cells or extracts [16,20], however, others pointed out the complexity caused by IgG-binding protein A and the potential advantages of using recombinant antigens [16,17,20]. Some investigators reported that patients with infection generally had higher antibody levels against purified proteins or recombinant antigens than healthy controls, and observed degrees of overlap between patients with infection and control subjects [8,13,33,44] similar to those reported here.…”

Section: Sensitivity (%)supporting

confidence: 66%

“…Although patients with infection had higher IgG titers than the control patients, the control patients also had significant IgG titers, some overlapping with the infected population. High IgG titers in noninfected individuals have been observed by others [5,8,13,17,[39][40][41][42][43] and may be related to the high rates of colonization with S aureus, especially among children. Most newborns first contact S aureus just after birth and the colonization rates of S aureus are high in children and adolescents (20%-24].…”

Section: A Predominant Pattern Of Antigens Recognized By Patients or mentioning

confidence: 66%

See 1 more Smart Citation

A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis

Nishitani

Beck

Rosenberg

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Because immunity against Staphylococcus aureus has not been fully elucidated, there is no diagnostic test to gauge how robust a patient's host response is likely to be. Therefore, we aimed to develop a test for specific antibodies in serum with diagnostic and prognostic potential. Questions/Purposes We describe the development and validation of a multiplex immunoassay for characterizing a patient's immune response against 14 known S aureus antigens, which we then used to answer four questions: (1) Do certain antigens predominate in the immune response against S aureus? (2) Is there a predominant pattern of antigens recognized by patients and mice with infections? (3) Is the immunoglobulin G (IgG) response to any single antigen a useful predictor of ongoing S aureus infection? (4) Does measurement of the combined response against all 14 antigens provide a better predictor of ongoing infection? Methods A case-control study was performed. Sera were collected from 35 consecutive patients with S aureus culture-confirmed (methicillin-sensitive S aureus or methicillin-resistant S aureus) musculoskeletal infections The institution of one or more of the authors (EMS, SLK, JLD, CAB) has received, during the study period, funding from the National Institutes of Health, NIAMS (Bethesda, MD, USA) and (EMS, SLK, JLD) the AOTrauma Clinical Priority Program (Davos, Switzerland). One of the authors certifies that he (JLD) or she or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000 from Telephus Medical LLC (San Diego, CA, USA) and an amount of less than USD 10,000 from Calorics Pharmaceuticals (Waltham, MA, USA). One of the authors certifies that he (EMS) or she or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000 from Telephus Medical LLC (San Diego, CA, USA). One of the authors certifies that he (SLK) or she or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of less than USD 10,000 from Surgical Excellence Healthcare Quality Consulting, and an amount of USD 10,000 to 100,000 from Sage Publications (Thousand Oaks, CA, USA) One of the authors certifies that he (CAB) or she or a member of his or her immediate family, has received or may receive payments or benefits, during the study period, an amount of USD 10,000 to 100,000 from the FDA (Silver Spring, MD, USA), and an amount of USD 10,000 to 100,000 from Boston Scientific (Marlborough, MA, USA), an amount of USD 10,000 to 100,000 from Lundbeck Inc (Deerfield, IL, USA), an amount of USD 10,000 to 100,000 from Patient-Centered Outcomes Research Institute (PCORI, Washington, DC, USA), and an amount of less than USD 10,000 from Auspex Pharmaceuticals (La Jolla, CA, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board mem...

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Section: Sensitivity (%)supporting

confidence: 66%

Section: A Predominant Pattern Of Antigens Recognized By Patients or mentioning

confidence: 66%

A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis

Nishitani

Beck

Rosenberg

et al. 2015

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

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“…The immune mechanisms that mediate long-lasting protection to S. aureus skin infections have remained elusive, especially since recurrences are common despite the generation of high titers of specific antibodies and memory αβ T cells (3,4). In the present study, we utilized S. aureus-susceptible IL-1β -/-mice with impaired neutrophil recruitment and IL-17 responses to elucidate host defense mechanisms that provide durable protection against an S. aureus skin reinfection.…”

Section: Discussionmentioning

confidence: 99%

“…The precise immune responses that protect against S. aureus skin infections are unclear, as nearly half of individuals with an S. aureus skin infection suffer a recurrence (2), despite the generation of high titers of specific antibodies and memory CD4 + T cells (3,4). Moreover, all prior S. aureus vaccines in humans that targeted antibody-mediated phagocytosis have lacked efficacy or resulted in increased mortality (5).…”

Section: Introductionmentioning

confidence: 99%

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

Dillen

Pinsker

Marusina³

et al. 2018

Journal of Clinical Investigation

112

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“…8 With the growing burden of S. aureus disease, increasing antibiotic resistance, and limited efficacy of decolonization protocols, 9,10 there is substantial interest in development of a S. aureus vaccine for use in high risk populations. Although an effective S. aureus vaccine remains elusive, [13][14][15][16][17][18] there is general consensus on a multi-antigen approach to vaccine development, which targets T and B cell responses to S. aureus cell surface components, virulence factors and toxins. 19 a-toxin and Panton-Valentine leukocidin (PVL) are 2 toxins of interest for a toxoid based approach that have shown efficacy in animal models.…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults

Landrum

Lalani

Niknian³

et al. 2017

Human Vaccines & Immunotherapeutics

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We conducted a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults to evaluate the safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens, recombinant a-toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV). 176 subjects were enrolled and randomized within 1 of 11 treatment cohorts: monovalent rAT or rLukS-PV dosages of 10, 25, 50, and 100 mg; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 mg; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 mg bivalent cohort received a second injection on Day 84 and were assessed on Days 98 and 112. Incidence and severity of reactogenicity and adverse events (AEs) were compared. Geometric mean serum concentrations (GMC) and neutralizing activity of anti-rAT and anti-rLukS-PV IgG were assessed. Reactogenicity incidence was significantly higher in vaccine than placebo recipients (77% versus 55%, respectively; p D 0.006). However, 77% of reactogenicity events were mild and 19% were moderate in severity. The AE incidence and severity were similar between the cohorts. All monovalent and bivalent rAT dosages resulted in a significant increase in the anti-rAT IgG and anti-rLukS-PV GMCs between day 0 and 28 compared with placebo, and persisted through Day 84. Exploratory subgroup analyses suggested a higher GMC and neutralizing antibody titers for the 50 mg monovalent or bivalent rAT and rLukS-PV dose as compared to the other doses. No booster effect was observed after administration of the second dose. We conclude that the rAT and rLukS-PV vaccine formulations were well-tolerated and had a favorable immunogenicity profile, producing antibody with neutralizing activity through day 84. There was no benefit observed with a booster dose of the vaccine.

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Towards the immune proteome of Staphylococcus aureus – The anti-S. aureus antibody response

Cited by 98 publications

References 149 publications

A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis

A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults

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