Projects - prof.dr.ir. GP (Gorben) Pijlman
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Non-coding flavivirus RNA as key target to engineer live-attenuated vaccines that are ‘safe-by-design’ (NWO-ENW M1) 2022 - 2026
Flaviviruses such as dengue, Zika, West Nile and tick-borne encephalitis are important human pathogens that pose a global health risk. Only a few flavivirus vaccines are available, mainly because it is difficult to generate vaccines that are safe and effective at the same time. We aim to engineer live-attenuated flaviviruses that are defective in the production of a non-coding viral RNA called ‘sfRNA’ that has been shown to be essential for viral pathogenicity. This research will not only increase our fundamental understanding of non-coding RNA in viral infections, but also contribute to development of novel designer vaccines that can help mitigate current and future flavivirus epidemics.
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Mosquito RNA vaccine (MORV) 2022
Vaccination of humans is not always possible for viral diseases transmitted by blood-feeding mosquitoes. This proposal is a proof-of-concept to ‘vaccinate’ mosquitoes using a self-replicating mosquito RNA vaccine (MORV). The MORV is a small synthetic RNA that can be rapidly tailored to any viral disease. This short project will engineer the MORV, study the mosquito immune response, and test if mosquitoes become resistant to Zika and West Nile virus. Eventually, MORV-vaccinated mosquitoes can be released into the environment to reduce virus transmission. The project is also important to establish the legal status of novel genomic techniques in renewed European legislation.
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Horizon 2020 Prevent-nCoV. Prevention of SARS-CoV-2 infection through development and clinical testing of a novel Virus Like Particle (VLP) vaccine. 2020-2022
https://cordis.europa.eu/project/id/101003608
Our aim is to perform pre-clinical and clinical evaluation of a Coronavirus vaccine candidate. The vaccine will be based on Virus-Like Particle (VLP) display of the SARS-CoV-2 Spike protein antigen. VLP display technology has been shown to significantly improve vaccine immunogenicity, longevity and efficacy, for a wide range of viral and parasite diseases in pre-clinical studies (including flu and malaria). The Spike antigen will be produced in Drosophila S2 insect cells, in E.coli or using baculovirus expression in Sf9 insect cells. The vaccine candidates will be tested pre-clinically using in vitro viral neutralisation assays and animal challenge models. Finally, a phase I/IIa study will be performed. This project is focused on delivering a scalable vaccine, ready for testing in the field, which has been shown to be safe in humans and effective in in vitro or animal models.
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RepliSAFE: Environmental safety of synthetic replicon particle vaccines – risk for RNA recombination with wildtype viruses. 2018 - 2022
TTW Biotechnology and Safety Programme - New and future Modern Biotechnology Techniques and Applications in relation to Environmental Safety
Vaccines are essential tools to control infectious disease outbreaks in humans, companion animals and livestock farming animals. Next generation vaccines based on self-replicating, so-called ‘replicon particles’ (RPs) are ‘safe by design’. RP vaccines are highly innovative and combine the advantages of a ‘replicating’ vaccine without the ability to spread and cause disease. Synthetic gene technology has dramatically accelerated the development of new RP vaccines (‘plug-and-play’ technology) and provides emergency preparedness for epidemics of novel and emerging pathogens such as Ebola and avian flu. The environmental safety profile of RP vaccines is a crucial aspect of the registration process by regulatory authorities, but the potential for recombination of the RP vaccine with naturally occurring wildtype viruses remains poorly studied. The RepliSAFE project will provide essential data on persistence and cell/tissue tropism of RP vaccines in laboratory animals, will study the potential for recombination with wildtype viruses in cell culture and animals, and lay out a risk assessment framework applicable to RP vaccines of the future.
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Uzootu (PE&RC One Health): Usutu virus in the Netherlands - Zoonotic potential and fitness trade-offs in birds and mosquitoes. 2018 - 2020
Usutu virus (USUV) is a highly pathogenic mosquito-borne virus of birds that was recently associated with neurological disease in humans. USUV is maintained in an enzootic mosquito–bird transmission cycle, with birds of 14 orders able to become infected. USUV has been circulating in Europe for over twenty years, but the first outbreak of USUV in the Netherlands was reported in September 2016. The true zoonotic potential of USUV, which is the ability to infect and cause disease in humans, is currently still unknown and needs to be investigated. The overall aim of this project is to gain insight into the zoonotic potential of contemporary USUV strains and to study the fitness trade-offs caused by pathogenicity mutations in the viral genome in mosquitoes and birds.
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ZikaRisk (ZonMw) 2017 -2021
Zika virus (ZIKV), a mosquito-borne flavivirus previously considered a zoonosis of limited importance to human health, is causing an epidemic of unprecedented scale in Middle/South America and the Caribbean. Urban ZIKV is transmitted in a cycle involving humans and mosquitoes, but maintenance in major areas of the world has involved non-human reservoir hosts. Previously undetected severe clinical complications (microcephaly, Guillain-Barre syndrome) form a major health concern, yet are poorly understood.
A One Health approach involving medical/veterinary/insect virologists and medical entomologists is essential 1) to determine the risk of disease in ZIKV-exposed patients in The Netherlands including the overseas territories, 2) to understand the explosive spread of ZIKV and possible introduction/establishment in the Netherlands, and 3) to allow risk assessment for ZIKV and other future arboviral outbreaks. We will determine the risk of ZIKV establishment based on prospective studies in travellers and vector competence studies in indigenous mosquitoes, and develop animal-free laboratory models to study ZIKV tropism and disease.
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ZIKAlliance (H2020 2017 - 2021) is a multinational and multi-disciplinary research consortium comprised of 52 partners worldwide and coordinated by Inserm, the French National Institute of Health and Medical Research. ZIKAlliance is funded by the European Union's Horizon 2020 Research and Innovation Programme. The project will investigate clinical, fundamental, environmental and social aspects of ZIKV infection. In particular, ZIKAlliance will focus on the impact of ZIKV infection during pregnancy and the natural history of ZIKV in humans and their environment. In collaboration with two other EC funded consortia (ZikaPLAN and ZIKAction), ZIKAlliance will also work on the development of a preparedness platform in Latin America and the Caribbean. https://zikalliance.tghn.org/
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VECTORIE (FP7 2009-2013) is an acronym for Vector-borne Risks for Europe: Risk assessment and control of West Nile and Chikungunya virus, and is a focused research project funded by the European Commission under the Seventh Framework Programme (FP7).
Both West Nile virus (WNV) and Chikungunya virus (CHIKV) are emerging vector-borne viruses that are transmitted??by mosquitoes (the vector) from one infected host to another.??They are known to cause West Nile disease and Chikungunya disease respectively in humans. In light of the increased risk of WNV and CHIKV outbreaks in Europe and the increasing notifications of the West Nile disease and Chikungunya fever cases in Europe, it has become imperative to assume a proactive approach to anticipate and deal with threats of mosquito-borne infections, such as WNV and CHIKV at the EU level.
Current WNV and CHIKV control strategies are based largely on vector control. The risk of WNV and CHIKV outbreaks in humans is not only determined by vector competence but also by their feeding behaviour. These factors have so far not been investigated for European vectors. It is not known whether European Culex pipiens mosquitoes transmit WNV to animals or humans. Therefore, defining vector competence and feeding behavior is essential in formulating and focusing a prevention plan. Culex pipiens mosquitoes will be used for studies on vector competence and compared to WNV-competent Culex pipiens from the US. These studies will be conducted by Wageningen University in their BSL3 facility.
