Publications by authors named "Rutger Schepp"

Antibodies in human milk protect infants against infections, but currently no assay is described that is able to simultaneously measure all 9 antibody isotypes and subclasses immunoglobulins in human fluids, such as human milk. Our cohort "Protecting against Respiratory tract Infections through human Milk Analysis" (PRIMA) is focused on the relation between the occurrence of respiratory infections during the first year of life and concentration of maternal antibodies in breastfeeding. We developed and successfully validated a multiplex assay that is able to measure all nine antibody isotypes and subclasses in human plasma and milk (regardeless of the pathogen specificity), using a small sample volume.

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Article Synopsis
  • The study investigates differences in antibody responses to SARS-CoV-2 between children and adults, focusing on various Fc-mediated functions like phagocytosis and natural killer cell activation over a 10-month period.
  • Results indicate that children exhibit similar, but potentially more durable, antibody responses, particularly in complement deposition, compared to adults, while natural killer cell activation was notably reduced in both groups.
  • Understanding these differences is important for developing tailored vaccination strategies against respiratory viruses, highlighting the need for age-specific insights in vaccine design.
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Neutralizing antibodies are considered a correlate of protection against severe human respiratory syncytial virus (HRSV) disease. Currently, HRSV neutralization assays are performed on immortalized cell lines like Vero or A549 cells. It is known that assays on these cell lines exclusively detect neutralizing antibodies (nAbs) directed to the fusion (F) protein.

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Antibodies to SARS-CoV-2 on the mucosal surfaces of the respiratory tract are understood to contribute to protection against SARS-CoV-2 infection. We aimed to describe the prevalence, levels, and functionality of mucosal antibodies in the general Dutch population. Nasal samples were collected from 778 randomly selected participants, 1-90 years of age, nested within the nationwide prospective SARS-CoV-2 PIENTER corona serosurvey in the Netherlands.

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Respiratory syncytial virus (RSV) is a common global respiratory virus that is increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults that has acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions.

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Article Synopsis
  • Respiratory Syncytial Virus (RSV) is especially dangerous for infants, particularly those born very preterm, and the standard prevention method, palivizumab, is costly and used mainly for high-risk newborns.
  • A study in the Netherlands found that palivizumab significantly reduced RSV infection rates in very preterm infants during their first year of life, with rates dropping from 48.3% to 18.9% for those receiving the prophylaxis.
  • The research suggests that while palivizumab is effective for very preterm infants, further studies are needed to understand non-compliance issues and to compare it with new treatments like nirsevimab to improve health outcomes for preterm infants.
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  • RSV infections are a leading cause of serious respiratory illnesses, especially in infants and the elderly, but there's no clear protective marker against the virus.
  • Evidence shows that antibody functions are crucial for immunity, but there's limited understanding of how these responses vary and last over time.
  • This study examined various antibody characteristics across different age groups and found that younger children have lower antibody-dependent natural killer cell activation (ADNKA) compared to adults, and older adults show boosted antibody responses after RSV infection that stabilize over time, highlighting the complexity of immune responses to RSV.
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Background: Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection.

Methods: We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who developed recurrent RSV infection.

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Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.

Methods: To determine whether a memory T cell response is being developed, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker analyses of peripheral blood samples from unvaccinated children and adults with mild-to-moderate COVID-19.

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Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization in infants. Underlying risk factors for RSV infection in the general population are not well understood, as previous work has focused on severe outcomes of infection in a clinical setting. Here we use RSV-specific IgG and IgA antibody measurements from two population-based cross-sectional serosurveys carried out in the Netherlands (n = 682) to classify children up to 5 years as seronegative or seropositive.

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Background: Assessing the duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a first priority to gauge the degree of protection following infection. Such knowledge is lacking, especially in the general population. Here, we studied changes in immunoglobulin isotype seropositivity and immunoglobulin G (IgG) binding strength of SARS-CoV-2-specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample.

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BackgroundBronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants.AimTo describe RSV epidemiology in children in the community in a high-income setting.MethodsWe used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records.

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Background: We aimed to detect SARS-CoV-2 serum antibodies in the general population of the Netherlands and identify risk factors for seropositivity amidst the first COVID-19 epidemic wave.

Methods: Participants (n=3207, aged 2-90 years), enrolled from a previously established nationwide serosurveillance study, provided a self-collected fingerstick blood sample and completed a questionnaire (median inclusion date 3 April 2020). IgG antibodies targeted against the spike S1-protein of SARS-CoV-2 were quantified using a validated multiplex-immunoassay.

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Background: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients.

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Background: Respiratory syncytial virus (RSV) generally causes mild disease but can cause severe infections in (premature) infants and elderly adults. Here, we studied RSV-specific antibody concentrations throughout life with emphasis on infants and chronic obstructive pulmonary disease (COPD) patients.

Methods: Sera (N = 2655) from 2 nationwide cross-sectional studies in the Netherlands including individuals aged 0-90 years were analyzed for IgG and IgA antibodies to RSV prefusion F, postfusion F, N, Ga, and Gb proteins and for antibody avidity in 42 COPD patients.

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Article Synopsis
  • RSV poses a significant health risk to older adults, yet there is limited research on how their immune systems respond to the virus, which complicates vaccine and treatment development.
  • In a study involving older adults (≥60 years) over three winters, researchers tracked immune responses by analyzing serum and nasal swabs for antibodies and cytokines during RSV infection and recovery.
  • The results showed increased antibody responses and local cytokine production in infected individuals, highlighting important immune mechanisms that could inform future RSV prevention and therapy strategies in older populations.
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Background: The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.

Methods: Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres.

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Objective: This study aimed to assess the safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccination in childhood-onset systemic lupus erythematosus (cSLE) patients.

Methods: Volunteer cSLE patients aged 9-20 years and healthy controls (HC) were enrolled to receive a two- or three-dose qHPV vaccination schedule from March 2014 to March 2016. Study visits were performed before the first dose, one month after the second and third doses and one year after the first dose.

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Article Synopsis
  • RSV (Respiratory syncytial virus) is a leading cause of severe respiratory infections in infants, highlighting the need for better understanding of maternal antibodies and their role in protection.
  • Antibody levels alone do not effectively correlate with protection against RSV; instead, the ability of antibodies to activate natural killer (NK) cells may be more critical.
  • The study suggests that the quality of antibodies, particularly their Fc-glycosylation status, affects NK cell activation and may play a significant role in protecting against severe RSV disease, indicating potential avenues for vaccine improvement.
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The bivalent human papillomavirus (HPV) vaccine is highly effective and induces robust serological responses. Using a Dutch prospective cohort initiated in 2009, including 744 vaccinated and 294 unvaccinated girls (1993-1994) who provide a vaginal self-swab sample, serum sample, and questionnaire yearly, we report a high, persisting antibody response up to 9 years after vaccination for vaccine types HPV-16 or HPV-18. Antibodies against nonvaccine HPV types 31, 33, 45, 52, and 58 were lower but still significantly higher than in unvaccinated individuals.

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Human respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in (premature) newborns and causes respiratory illness in the elderly. Different monoclonal antibody (MAb) and vaccine candidates are in development worldwide and will hopefully become available within the near future. To implement such RSV vaccines, adequate decisions about immunization schedules and the different target group(s) need to be made, for which the assessment of antibody levels against RSV is essential.

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Background: In this cohort study, we examined antibody levels and avidity after a two-dose schedule (0, 6 months) of the bivalent HPV-vaccine in girls routinely vaccinated in the Dutch HPV-vaccination program, up to 2 years following vaccination.

Methods: A blood sample at 7, 12 and 24 months after the first dose and questionnaire data were collected (n = 56). HPV type-specific antibody concentrations (lU/ml) against seven types (HPV16/18/31/33/45/52/58) were assessed using a validated virus-like particles (VLP) multiplex immunoassay.

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Asylum seekers are a vulnerable population for contracting infectious diseases. Outbreaks occur among children and adults. In the Netherlands, asylum seeker children are offered vaccination according to the National Immunization Program.

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