AIROPico is an exchange project offering 21 researchers the possibility to move sector and country to provide, absorb and implement new knowledge. The exchanges will aim for implementation of new knowledge in a professional industrial-academic environment in the field of virology. The exchanges will have a particular focus on virus-host interaction, detection and defence of picornaviruses.
The respective research teams will be enforced by 5 newly recruited experienced researchers offering complementary expertise to the consortium.
WPL: Dirk Jochmans
Generation of human monoclonal antibodies as potential therapeutic antibodies.
Fully human monoclonal antibodies will be generated and tested with replication competent virus to select mono-specific or cross-neutralising monoclonal antibodies. Next the epitopes will be identified. The most interesting monoclonal antibodies will be characterized in molecular detail within WP1. Main location: currently unknown
Identification small molecule compounds with the capacity to inhibit virus entry.
Initially our research will target the most clinically relevant and wide-spread virus types (CBV3 and EV71). A compound library of ~10.000 synthetic and semi-synthetic compounds (derived from natural products) will be screened with live virus to allow for discovery of inhibitors of all processes within the virus replication cycle. The aim is to obtain compounds with broad-spectrum anti-picorna activity. The selected compounds and their working-mechanism will be characterized which in turn will provide novel insights into the replication strategy of picornaviruses. Main location: REGA
WPL: Sarah Butcher
Determination of specific neutralizing epitopes for generation of therapeutic moAbs and proteins to be used in diagnostic assays.
We will align picornaviral sequences to identify common epitopes/antigens which will be synthesized and used as antigen for antibody production for diagnostics or therapy. Main locations: TU
Studying virus structure, in relation to (known) receptors and human monoclonal antibodies.
By determining the 3D structure of selected clinical-relevant virus isolates by 3-dimensional electron microscopy and image processing (3DEM), X-ray crystallography and EM to reveal the position of the epitope; the exact 3D position on the virus bound by the receptor. Once the epitope is known, interfering antibodies can be designed with neutralising capacities. In addition, entry studies at AMC/REGA using light and electron cryo-tomography on infected cells will be performed to unravel the exact mechanism of the viral life cycle. Main location: UH
Setting up standardized models for virus-host interaction by the use of human organ cultures (3D cultures).
With 3D cultures of both human epithelial airway and human gut, primary infection with picornaviruses can be mimicked and studied providing valuable information on virus entry, primary target cells and the relevance of entry receptors. In addition, the developed antibodies can be tested in vitro for neutralising and inhibitory properties. Main location: AMC
Standardizing protocols for viral cloning, and generate infectious clones for all types.
We will generate T7 promotor-tagged full-length PCR clones of selected picornaviral sequences which are capable of replicating. We will also use this technique to generate infectious virus variants. Main location: TU
WPL: Petri Susi .
Identification of proteins that can be used for a platform on development of Point of Care (POC) testing.
Within this workpackage the optimal virus molecules will be identified for protein production and antibody binding. These viral proteins will be used in company-based point of care applications for rapid detection of picornaviruses in clinical samples. The aim is that the specificity of these rapid point of care tests can compete with existing routine picornaviral RT-qPCR tests. Main location: TU.
Development of picornavirus POC test.
At this time there is no POC test available for picornavirus detection due to the plethora of virus subtypes. Information from WP1 on virus surface epitopes will be used for the development of the POC test which involves coating nanoparticples with viral antigens. The developed test will be compared to conventional ELISA and the end-product will be sold under the trade name mariPOC®. The consortium will start with the development of a POC test for rhinoviruses and will expand this to other picornaviruses. Main location: ArcDia
Development of fast molecular typing methods.
The available clinical sample collection will be used to develop fast and more sensitive and specific genotyping assays for picornaviruses from clinical samples. Main locations: TIB, TU
Evaluation of newly developed tests on virus prototypes and on patient samples.
Main location: AMC
The AIROPico Project
AIROPico stands for Academic Industry R&D Opportunities
This Research Project will generate more knowledge on commonly encountered infections of human picornaviruses like the common cold. This knowledge will give us more insight in these virus infections and the disease they cause. Based on these insights effective antiviral treatments will be developed.
AIROPico is an Industry-Academia Partnerships and Pathways project (IAPP). It will provide interdisciplinary education and training to company researchers and university scientists. Twenty-one staff exchanges will enforce the collaboration within the Consortium on picornavirus biology, diagnostics and therapy development.