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Projects - dr. BHG (Barry) Rockx

  • In vitro and in vivo models to study tick-borne viruses

    https://www.wur.nl/nl/onderzoek-resultaten/onderzoeksprojecten-lnv/soorten-onderzoek/kennisonline/teken-overdraagbare-virussen.htm

    Ticks can transmit a wide-range of pathogens (viruses, bacterial and parasites) that can damage the health of animals and humans. New tick-borne pathogens continue to be discovered, and existing pathogens expand their geographic range, including in the Netherlands. In addition to new viruses, new tick species may also be introduced in the Netherlands through migratory birds, which may harbour exotic viruses. Expertise in the transmission and pathogenesis of tick-borne pathogens is important because ongoing changes in climate and land-use will lead to further spread and introduction of different tick-species and the potential pathogens they carry.

    The goal of this project is to develop expertise on tick-borne viruses under biosafety level 3 conditions using both cell culture and animal models which will allow us to study the role of ticks and specifically the tick bite in the transmission and pathogenesis of emerging tick-borne viruses.

  • In-vitro and ex-vivo systems: Development of an ovine placental barrier to study arbovirus infection in vitro

    https://www.wur.nl/nl/onderzoek-resultaten/onderzoeksprojecten-lnv/soorten-onderzoek/kennisonline/in-vitro-en-ex-vivo-systemen-1.htm

    Many arboviruses are known to cause disease in ruminants like cattle, goats, and sheep. Several of these viruses infect and subsequently cross the placenta of pregnant animals, frequently resulting in abortion, malformation, or stillbirth of the fetus. The exact mechanisms of this transplacental transmission remain elusive. Whereas for the human placenta in vitro models are in place to study the placental barrier and its susceptibility to different pathogens, in vitro models mimicking the ruminant placental barrier, which has distinct anatomy, have not yet been described. In this project, we recapitulate the ovine placental barrier by co-culturing primary maternal epithelial cells, isolated from the placenta of a pregnant sheep, and fetal trophoblast cells and use Rift Valley fever virus as a prototype pathogen for infection experiments.

  • VECTORED

    A key gap in knowledge for the development of interventions against arbovirus infection is whether or not vaccines and/or antivirals protect against infection by vector bite – the natural route of arbovirus infection. There is accumulating data suggesting that virus challenge via a vector bite may differ from needle inoculation and requires higher vaccine efficacy because of immune-modulating substances and pro-viral factors in vector saliva. However, solid in vivo evidence for this phenomenon is currently lacking, because these experiments are technically and logistically highly challenging. We propose to develop vector-borne challenge models for a range of vectors (mosquitoes, and ticks) and different emerging medically important arboviruses on the list of ISIDORe priority preparedness pathogens (West Nile virus (WNV), and tick-borne encephalitis virus (TBEV)). While, we will perform vector-challenge studies with rodents in the current project, our consortium has the facilities and expertise to expand to larger target animal species, including livestock if relevant (e.g., birds for WNV and JEV, swine for JEV, lambs for RVFV, sheep and goats for TBEV) and wildlife (wild rodents for TBEV, wild birds for WNV). Following vector competence confirmation for specific arboviruses and establishing optimal vector feeding conditions on laboratory mice, we will compare the viral and antibody kinetics and disease progression (pathogenesis) following vector-borne transmission challenge with that of the Gold Standard needle inoculation of the different viruses.
    Upon establishing these models, these challenge models will be available for the ISIDORe catalogue of services for preclinical evaluation of intervention studies. In addition, the models can be used to study the role of the vector in arboviral infection. Finally, by establishing these models for a range of vectors, this will also be a platform for preparing for arbovirus X.