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September 2003 - present
Publications
Publications (55)
Mumps virus is a highly transmissible pathogen that is effectively controlled in countries with high vaccination coverage. Nevertheless, outbreaks have occurred worldwide over the past decades in vaccinated populations. Here we analyse serological data from outbreaks of mumps virus genotype G among college students in the Netherlands over the perio...
Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based...
Influenza-like illness (ILI) can be caused by a range of respiratory viruses. The present study investigates the contribution of influenza and other respiratory viruses, the occurrence of viral co-infections, and the persistence of the viruses after ILI onset in older adults. During the influenza season 2014–2015, 2366 generally healthy community-d...
[This corrects the article DOI: 10.3389/fimmu.2022.817876.].
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 bei...
Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing antibodies against both the mumps...
Waning of the mumps virus (MuV)-specific humoral response after vaccination has been suggested as a cause for recent mumps outbreaks in vaccinated young adults, although it cannot explain all cases. Moreover, CD8+ T cells may play an important role in the response against MuV; however, little is known about the characteristics and dynamics of the M...
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 be...
Mumps is nowadays re-emerging despite vaccination. The contribution of T cell immunity to protection against mumps has not been clearly defined. Previously, we described a set of 41 peptides that were eluted from human leukocyte antigen (HLA) class I molecules of mumps virus (MuV)-infected cells. Here, we confirmed immunogenicity of five novel HLA-...
Nowadays, mumps is re-emerging in highly vaccinated populations. Waning of vaccine-induced immunity plays a role, but antigenic differences between vaccine and mumps outbreak strains could also contribute to reduced vaccine effectiveness. CD8+ T cells play a critical role in immunity to viruses. However, limited data are available about sequence va...
Mumps is nowadays re-emerging despite vaccination. The contribution of T cell immunity to protection against mumps has not been clearly defined. Previously, we described a set of 41 peptides that were eluted from human leukocyte antigen (HLA) class I molecules of mumps virus (MuV)-infected cells. Here, we confirmed immunogenicity of five novel HLA-...
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...
Background
Breakthrough infections of measles and mumps have raised concerns about the duration of vaccine-induced immunity, which might be improved by a third dose of measles-mumps-rubella vaccine (MMR3).
Methods
Here we compared (IgG) antibody levels against measles, mumps, and rubella in blood samples of 9-year-old children and young adults (18...
Background:
The re-emergence of mumps among vaccinated young adults has become a global issue. Besides waning of antibody responses, suboptimal induction of T cell responses may reduce protection. Recently, we observed a dominant polyfunctional CD8+ T cell response after natural mumps virus (MuV) infection that was not present after vaccination. U...
Recent outbreaks of mumps among vaccinated young adults have been reported worldwide. Humoral responses against mumps virus (MuV) are well characterized, although no correlate of protection has been elucidated, stressing the need to better understand cellular MuV-specific immunity. In this study, we identified the first MuV T cell epitope, which is...
Tick-borne encephalitis and West Nile fever are endemic flavivirus diseases in Europe. Climate change, virus evolution, and social factors may increase the risk of these flavivirus infections and may lead to the emergence of other flaviviruses in Europe that are endemic in (sub)tropical regions of the world. Control of the spread of flaviviruses is...
Background:
Similar to other recent mumps genotype G outbreaks worldwide, most mumps patients during the recent mumps genotype G outbreaks in the Netherlands had received 2 doses of measles, mumps and rubella (MMR) vaccine during childhood. Here, we investigate the capacity of vaccine-induced antibodies to neutralize wild type mumps virus strains,...
In the last decade, mumps virus (MuV) causes outbreaks in highly vaccinated populations. Sub-optimal T cell immunity may play a role in the susceptibility to mumps in vaccinated individuals. T cell responses to mumps virus have been demonstrated, yet the quality of the MuV-specific T cell response has not been analyzed using single cell immunologic...
Lyme disease is the most common tick-borne illness in the Northern hemisphere and is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. A first sign of Borrelia infection is a circular skin rash, erythema migrans, but it can develop to more serious manifestations affecting skin, nervous system, joints, and/or heart. The marked in...
In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases, young adults were affected who have acquired immunity against mumps solely by vaccination and not by previous wild-type mumps virus infection. To investigate mumps-specific antibody levels, functionality and dynamics duri...
Last decades, the number of routine childhood vaccinations has increased considerably, which consequently has led to multiple vaccine injections per consultation. Implementation of additional vaccines will probably lead to more than 2 vaccine injections per consult, which might be a barrier for parents to vaccinate their child. A decrease in vaccin...
Effective polysaccharide(conjugate) vaccines against Neisseria meningitidis serogroups A, C, W, and Y have been widely used, but serogroup B meningococci remain a major cause of severe invasive meningococcal disease (IMD) worldwide, especially in infants. Recently, a vaccine, 4CMenB (Bexsero®), containing three recombinant proteins, and outer membr...
The respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness (LRI) in infants worldwide. Also persons with heart/lung disease or an immunodeficiency disorder, and the elderly are at increased risk for severe LRI upon RSV infection. Although there is at present no licensed RSV vaccine available, it is a priority target...
An improved detergent-free process has been developed to produce vaccine based on native outer membrane vesicles (NOMV) against Neisseria meningitidis serogroup B. Performance was evaluated with the NonaMen vaccine concept, which provides broad coverage based on nine distinct PorA antigens. Scalable aseptic equipment was implemented, replacing unde...
Genetic modifications of the trivalent RL production strains. The RL strains are non-encapsulated variants of strain H44/76, in which rmpM (R) and lpxL1 (L) genes have been disrupted to improve yield and attenuate LPS toxicity (galE truncated lpxL1-LPS). Each RL strain has 3 cloning sites for recombinant antigens. The NonaMen vaccine concept (nonav...
Real-time stability of bulk NOMV. Results of an ongoing stability study are shown at 0, 3, 6 and 12 months after production. They are presented as A) Quality Control tests for general stability aspects and B) Stability of selected PorA epitopes. Results are highly reproducible throughout the study, as confirmed by trend analysis, indicating that th...
The respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness (LRI) in infants worldwide. Also persons with heart/lung disease or an immunodeficiency disorder, and the elderly are at increased risk for severe LRI upon RSV infection. Although there is at present no licensed RSV vaccine available, it is a priority target...
Despite the widespread use of polysaccharide and conjugate vaccines against disease caused by several serogroups of Neisseria meningitidis, vaccines targeting meningococci expressing the serogroup B capsule (MenB) have focused on subcapsular antigens, due to crossreactivity of the polysaccharide with human glycoproteins. Protein vaccines composed o...
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Fever has been reported as the most common adverse event after vaccination in infants and children. For this reason it is important that, prior to clinical testing of a new vaccine, change in body temperature following vaccination is tested carefully in nonclinical animal studies. Since both the timing and the height of the temperature peak after v...
The first meningococcal serogroup C (MenC) conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC d...
Hepatitis B is a serious public health problem. Worldwide three different levels of hepatitis B endemicity (high, intermediate and low) can be distinguished. Areas with different levels of endemicity require tailored vaccination strategies to fit the needs for individuals at risk and/or countries, depending on the infection risk per age group, vacc...
As reported in a recent issue of Eurosurveillance, a mumps outbreak is ongoing in the Netherlands despite high vaccination coverage of 90-95% [1]. The reported mumps cases are restricted to geographic regions with a high percentage of residents who are members of a religious community that rejects vaccination. Consequently, two thirds of the mumps...
Cytarabine (ara-C) is a key drug in the treatment of acute leukemia. Resistance to ara-C might be circumvented by the use of other deoxynucleoside analogs.
Using the MTT assay, we determined in vitro sensitivity and cross-resistance to deoxynucleoside analogs in 362 acute leukemia samples from untreated children and 32 normal bone marrow mononuclea...
A variety of antigens that display a highly tissue-specific expression pattern have recently found to be also expressed in medullary thymic epithelial cells (mTEC). This unique feature of mTEC plays an important role in preventing hazardous autoimmune responses through thymic tolerization of T-cell subsets directed against autoantigens but could al...
Investigation of the predictive value of a radiosurgery-relevant treatment of glioblastoma spheroids. Organotypic multicellular spheroids were cultured and irradiated (20 Gy). Morphology, apoptosis and immunohistochemical expression of p53, p21, MIB-1, TGF-beta and VEGF were examined 4 h, 24 h, 7 days, and 14 days following treatment. Cell prolifer...
To determine the potential of aplidin as a cytotoxic agent in pediatric leukemia, we tested bone marrow (BM) and peripheral blood (PB) samples (n=72) of children with different types of leukemia and healthy children in the methyl-thiazol-tetrazolium assay. Also, we compared these results with other cytotoxic drugs. Aplidin was cytotoxic in vitro at...
Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation.
Tumour specimens of glioblastoma multiforme patients (n = 16) were initiated as OMS. Following 20 Gy gamma-irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by micro-electrode pO2 measurem...
Bone marrow and peripheral blood samples from 362 patients with acute lymphoblastic leukaemia (ALL) proliferating cell and 90 patients with acute myeloid leukaemia (AML) were analysed for S-phase fractions, Ki67 antigen, and proliferating cell nuclear antigen expression. The S-phase fractions were correlated with in vitro drug resistance to 15 diff...
Radiotherapy plays a major role in the management of brain tumors, together with surgical resection and more recently, chemotherapy. Improved efficacy of radiotherapy, ranging from novel techniques of radiotherapy to combination with (new) chemotherapeutic drugs or agents that selectively target tumor cells, are currently being explored and offer s...
The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because recent studies on Daunorubicin in liposomes in the...
Since it is difficult to study the dynamic biological aspects of brain tumour invasion using histological sections of surgical biopsy and autopsy tissues, various laboratory systems have been devised. Animal models are less than ideal as chemically-induced brain tumours suffer from the fact that they have a low incidence and a long latency, while t...
The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS i...
Cluster of differentiation 44 (CD44) is a broadly distributed group of glycoproteins that are involved in many functions related to cell-cell and cell-matrix interactions. In the present study, the expression of the standard form of CD44 (CD44s) and of CD44 variants (CD44v) was explored immunohistochemically on frozen sections of various areas of t...
Fresh human glioma tissue can be cultured on agarose to form organotypic multicellular spheroids (OMS). The major advantage of OMS is the preservation of the cellular heterogeneity and the tumour architecture, which is lost in conventional monolayer cultures. The present study was undertaken to assess the possibilities of storing frozen OMS from se...
In the present study organotypic multicellular spheroids (OMS) were used to study the effects of chemotherapeutic agents on malignant gliomas. Compared with the frequently used cell line models, OMS have several advantages with respect to the preservation of the cellular heterogeneity and the structure of the original tumour. OMS prepared from seve...
Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of CD44 variant exon encoded sequences (CD44v) in pri...
Gliomas, as well as other solid tumours, contain tumour stroma composed of connective tissue, macrophages, capillaries and other non-cellular constituents. Therefore, a homogeneous culture of tumour cells alone, as is often used as a culture model for gliomas, is not ideal to study all aspects of gliomas. In the present study we describe an alterna...
Knowledge about lymphokine-activated killer (LAK) cell infiltration and LAK cell cytotoxicity is essential to improve the effectiveness of LAK cell therapy against gliomas. In the present study, organotypic multicellular spheroids (OMS) of glioma tissue were used as a culture model to study the effects of LAK cells on gliomas. Compared to tumour ce...
A M(r) 110,000 protein (p110) is overexpressed in P-glycoprotein-negative multidrug-resistant tumor cell lines of different histogenetic origins. These cell lines show an ATP-dependent drug accumulation defect, suggesting the presence of drug transporter molecules different from P-glycoprotein. Immunohistochemical staining with a p110-specific mono...
