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Search Results: 1 - 10 of 200615 matches for " Gorben P. Pijlman "
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Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells
Stefan W. Metz,Joy Gardner,Corinne Geertsema,Thuy T. Le,Lucas Goh,Just M. Vlak,Andreas Suhrbier,Gorben P. Pijlman
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002124
Abstract: The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs) in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 μg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Réunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.
West Nile Virus: High Transmission Rate in North-Western European Mosquitoes Indicates Its Epidemic Potential and Warrants Increased Surveillance
Jelke J. Fros?,Corinne Geertsema?,Chantal B. Vogels?,Peter P. Roosjen?,Anna-Bella Failloux?,Just M. Vlak?,Constantianus J. Koenraadt?,Willem Takken?,Gorben P. Pijlman
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0003956
Abstract: Background West Nile virus (WNV) is a highly pathogenic flavivirus transmitted by Culex spp. mosquitoes. In North America (NA), lineage 1 WNV caused the largest outbreak of neuroinvasive disease to date, while a novel pathogenic lineage 2 strain circulates in southern Europe. To estimate WNV lineage 2 epidemic potential it is paramount to know if mosquitoes from currently WNV-free areas can support further spread of this epidemic. Methodology/Principal Findings We assessed WNV vector competence of Culex pipiens mosquitoes originating from north-western Europe (NWE) in direct comparison with those from NA. We exposed mosquitoes to infectious blood meals of lineage 1 or 2 WNV and determined the infection and transmission rates. We explored reasons for vector competence differences by comparing intrathoracic injection versus blood meal infection, and we investigated the influence of temperature. We found that NWE mosquitoes are highly competent for both WNV lineages, with transmission rates up to 25%. Compared to NA mosquitoes, transmission rates for lineage 2 WNV were significantly elevated in NWE mosquitoes due to better virus dissemination from the midgut and a shorter extrinsic incubation time. WNV infection rates further increased with temperature increase. Conclusions/Significance Our study provides experimental evidence to indicate markedly different risk levels between both continents for lineage 2 WNV transmission and suggests a degree of genotype-genotype specificity in the interaction between virus and vector. Our experiments with varying temperatures explain the current localized WNV activity in southern Europe, yet imply further epidemic spread throughout NWE during periods with favourable climatic conditions. This emphasizes the need for intensified surveillance of virus activity in current WNV disease-free regions and warrants increased awareness in clinics throughout Europe.
Low Temperature-Dependent Salmonid Alphavirus Glycoprotein Processing and Recombinant Virus-Like Particle Formation
Stefan W. Metz, Femke Feenstra, Stephane Villoing, Marielle C. van Hulten, Jan W. van Lent, Joseph Koumans, Just M. Vlak, Gorben P. Pijlman
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025816
Abstract: Pancreas disease (PD) and sleeping disease (SD) are important viral scourges in aquaculture of Atlantic salmon and rainbow trout. The etiological agent of PD and SD is salmonid alphavirus (SAV), an unusual member of the Togaviridae (genus Alphavirus). SAV replicates at lower temperatures in fish. Outbreaks of SAV are associated with large economic losses of ~17 to 50 million $/year. Current control strategies rely on vaccination with inactivated virus formulations that are cumbersome to obtain and have intrinsic safety risks. In this research we were able to obtain non-infectious virus-like particles (VLPs) of SAV via expression of recombinant baculoviruses encoding SAV capsid protein and two major immunodominant viral glycoproteins, E1 and E2 in Spodoptera frugiperda Sf9 insect cells. However, this was only achieved when a temperature shift from 27°C to lower temperatures was applied. At 27°C, precursor E2 (PE2) was misfolded and not processed by host furin into mature E2. Hence, E2 was detected neither on the surface of infected cells nor as VLPs in the culture fluid. However, when temperatures during protein expression were lowered, PE2 was processed into mature E2 in a temperature-dependent manner and VLPs were abundantly produced. So, temperature shift-down during synthesis is a prerequisite for correct SAV glycoprotein processing and recombinant VLP production.
Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells
Stefan W Metz, Corinne Geertsema, Byron E Martina, Paulina Andrade, Jacco G Heldens, Monique M van Oers, Rob W Goldbach, Just M Vlak, Gorben P Pijlman
Virology Journal , 2011, DOI: 10.1186/1743-422x-8-353
Abstract: Expression in the presence of either tunicamycin or furin inhibitor showed that a substantial portion of recombinant intracellular E1 and precursor E3E2 was glycosylated, but that a smaller fraction of E3E2 was processed by furin into mature E3 and E2. Deletion of the C-terminal transmembrane domains of E1 and E2 enabled secretion of furin-cleaved, fully processed E1 and E2 subunits, which could then be efficiently purified from cell culture fluid via metal affinity chromatography. Confocal laser scanning microscopy on living baculovirus-infected Sf21 cells revealed that full-length E1 and E2 translocated to the plasma membrane, suggesting similar posttranslational processing of E1 and E2, as in a natural CHIKV infection. Baculovirus-directed expression of E1 displayed fusogenic activity as concluded from syncytia formation. CHIKV-E2 was able to induce neutralizing antibodies in rabbits.Chikungunya virus glycoproteins could be functionally expressed at high levels in insect cells and are properly glycosylated and cleaved by furin. The ability of purified, secreted CHIKV-E2 to induce neutralizing antibodies in rabbits underscores the potential use of E2 in a subunit vaccine to prevent CHIKV infections.Chikungunya virus (CHIKV) is an arthropod-borne (arbo)virus that causes epidemics in Africa, India and South-East Asia [1]. Recent outbreaks in Italy in 2007 [2] and autochthonous transmission events in France in 2010 [3] exemplify the threat of continued spread of CHIKV in the Western world, which correlates with the concurrent expanding distribution of its insect vector. CHIKV is maintained in a sylvatic transmission cycle of mosquitoes, rodents and primates, with Aedes aegyti as the primary vector. However, the responsible vector causing the severe CHIKV epidemic on the Reunion Islands in 2005/2006 was Ae. albopictus [4]. This vector switch made the virus endemic in more temperate regions and resulted in the first European cases (Italy, 2007) of transmission by local
A Heritable Antiviral RNAi Response Limits Orsay Virus Infection in Caenorhabditis elegans N2
Mark G. Sterken, L. Basten Snoek, Kobus J. Bosman, Jikke Daamen, Joost A. G. Riksen, Jaap Bakker, Gorben P. Pijlman, Jan E. Kammenga
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089760
Abstract: Orsay virus (OrV) is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi). However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.
Recombinant Modified Vaccinia Virus Ankara Expressing Glycoprotein E2 of Chikungunya Virus Protects AG129 Mice against Lethal Challenge
Petra van den Doel,Asisa Volz,Jouke M. Roose,Varsha D. Sewbalaksing,Gorben P. Pijlman,Ingeborg van Middelkoop,Vincent Duiverman,Eva van de Wetering,Gerd Sutter,Albert D. M. E. Osterhaus,Byron E. E. Martina
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003101
Abstract: Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.
Factorization and Universality in Azimuthal Asymmetries
F. Pijlman
Physics , 2004,
Abstract: The theoretical status on transverse momentum dependent factorization in semi-inclusive DIS and Drell-Yan is not clear in contrast to claims in the literature in which gauge links only at one loop were considered explicitly. Recent obtained results beyond this order questions the validity of these claims and will be briefly discussed. Possible input from experiments to solve these matters will be outlined.
Comparison of relativistic bound-state calculations in Front-Form and Instant-Form Dynamics
B. L. G. Bakker,M. van Iersel,F. Pijlman
Physics , 2002, DOI: 10.1007/s00601-003-0006-2
Abstract: Using the Wick-Cutkosky model and an extended version (massive exchange) of it, we have calculated the bound states in a quantum field theoretical approach. In the light-front formalism we have calculated the bound-state mass spectrum and wave functions. Using the Terent'ev transformation we can write down an approximation for the angular dependence of the wave function. After calculating the bound-state spectra we characterized all states found. Similarly, we have calculated the bound-state spectrum and wave functions in the instant-form formalism. We compare the spectra found in both forms of dynamics in the ladder approximation and show that in both forms of dynamics the O(4) symmetry is broken.
Cortisol-Induced Increases of Plasma Oxytocin Levels Predict Decreased Immediate Free Recall of Unpleasant Words
Mattie Tops,Femke T. A. Buisman-Pijlman,Maarten A. S. Boksem,Albertus A. Wijers
Frontiers in Psychiatry , 2012, DOI: 10.3389/fpsyt.2012.00043
Abstract: Cortisol and oxytocin have been shown to interact in both the regulation of stress responses and in memory function. In the present study we administered cortisol to 35 healthy female subjects in a within-subject double-blind placebo-controlled design, while measuring oxytocin levels, adrenocorticotropic hormone (ACTH) levels, and free recall of pleasant and of unpleasant words. We found that cortisol administration suppressed ACTH levels and (1) induced a decrease in oxytocin associated with ACTH suppression and (2) an increase in oxytocin that was independent from ACTH suppression. This cortisol-induced increase in plasma oxytocin was associated with a selective decrease in immediate free recall of unpleasant words from primacy positions. The present results add to evidence that cortisol-induced increases in oxytocin could mediate some of the effects of stress and cortisol on memory, and possibly play a role in the regulation of the hypothalamo-pituitary–adrenal stress response. This mechanism could significantly impact affective and social behaviors, in particular during times of stress.
The impact of a cancer Survivorship Care Plan on gynecological cancer patient and health care provider reported outcomes (ROGY Care): study protocol for a pragmatic cluster randomized controlled trial
Lonneke V van de Poll-Franse, Kim AH Nicolaije, Maria C Vos, Johanna MA Pijnenborg, Dorry Boll, Olga Husson, Nicole PM Ezendam, Erik A Boss, Ralph HM Hermans, Karin CM Engelhart, Joke E Haartsen, Brenda M Pijlman, Harrie WH Feijen, Helena JMM Mertens, Willem E Nolting, Johannes J van Beek, Jan A Roukema, Roy FPM Kruitwagen
Trials , 2011, DOI: 10.1186/1745-6215-12-256
Abstract: A web-based patient registration system 'Registrationsystem Oncological GYnecology' (ROGY) is used by gynecologists in the South of the Netherlands since 2006. A personalized SCP can automatically be generated out of ROGY. In this pragmatic cluster randomized controlled trial, 12 hospitals are randomized to either 'usual care' or 'SCP care'. In patients with 'usual care', the gynecologist provides care as usual. In patients with 'SCP care', information about the tumor stage and treatment is personally discussed with the patient and a document is handed to the patient. Prospectively, all patients diagnosed with endometrial or ovarian cancer in the participating hospitals will be approached for study participation. Patients will complete questionnaires after surgery, and before additional treatment, and after 6, 12, 18 and 24 months. In addition, health care providers will be asked their opinion about implementation of SCP care. Primary outcome is defined as patient satisfaction with information provision and care. Secondary outcomes are illness perception, health-related quality of life, health care use, prevalence, course and referral rate of survivors with psychosocial distress, and health care providers' evaluation of SCP care.The ROGY Care trial will help to gain insight into the impact of SCP care on patient reported outcomes, and on the evaluation of cancer survivors and health care providers of the different elements of the SCP. Therefore, results will contribute to efforts to improve quality of care for cancer survivors.Trial Registration: http://www.ClinicalTrials.gov webcite. Identifier: NCT01185626Medical Research Ethics Committee Reference Number: NL33429.008.10 Grant Reference Number: UVT2010-4743Due to earlier diagnoses and improved treatments, the number of cancer survivors is rapidly increasing in the Western world. In 2000, there were about 400,000 cancer survivors in The Netherlands, and this number is expected to increase to 700,000 in 2015 [1]. Ne
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