Work Packages

There are several stages within the HONOURs project at which ethical approvals are needed. The HONOURs ethical board will guide and guard ethical issues taking local and international legislations into account. An independent Ethics Advisor will oversee the implementation of the ethical concerns:  Prof dr. Laurent Kaiser, professor of medicine at the University of Geneva, Head of the Division of Infectious Diseases and Director of the Laboratory of Virology at the Geneva University Hospitals.

In case of emerging or re-emerging pathogen epidemics, detection has always been a major bottleneck delaying efficient outbreak management, including containment and treatment of infected individuals. For exactly this reason an Outbreak Antenna team will be installed within HONOURs, which consists of 11 ESRs, guided by 8 senior scientists. The team will monitor whether there are suspicions of new entries, or unexpected infections in their fields. At 7 sites the Outbreak Antenna will be operational: 3 sites to identify outbreaks in animals (Friedrich-Loeffler-Institut, Germany; Institute for Virology and Immunology, Switzerland; MSD Animal Health, the Netherlands) and 4 hospital sites to identify outbreaks in humans (Academic Medical Center, the Netherlands; KU Leuven, Belgium; Universität Bern, Institut für Infektionskrankheiten, Switzerland; Charité - Universitätsmedizin Berlin, Germany).

An outbreak can be of viral or bacterial origin. Identification of bacteria involved is in most cases possible via culture, and/or 16S rRNA sequencing or mass spectrometry approaches. Identification of unknown viruses is often more difficult since there are no conserved sequences shared by all viruses that can be used for identification. In addition, the viral load can vary and the viral genome load is often low in comparison to the total genomic material in a sample. Therefore novel complex state-of-the-art techniques have to be applied that can amplify and sequence virus genome fragments. These techniques can be summarized as viral metagenomics.

Once an association between disease and a novel virus has been established HONOURs will culture the virus, exploiting all primary cell culture approaches which are currently available and operational at the labs of the various beneficiaries.

Nowadays molecular approaches combined with powerful metagenomics sequencing methods allow the identification of previously unknown viruses in clinical samples, and a virus culture amplification step is no longer required. Without a culture system Koch’s postulates and the involvement in disease can however not be proven. As a result the quest for involvement in disease is determined via association with disease. This can be determined via 1) higher frequency of the virus in infected subjects compared to controls and 2) seroconversion to the agent during the course of the disease.

Notification of outbreaks identified in HONOURs is essential. In case of an outbreak the Awareness team of HONOURs together with the Supervisory board will coordinate the communication with the site of the outbreak, the hospital(s), the government and other stakeholders.

WP7 concerns the management of the project, the dissemination and exploitation of the project progress and results. The coordinator of HONOURs will monitor the progress in the work packages with respect to objectives and deliverables, is involved in-, and will coordinate all the key scientific, administrative and financial decision in the project and ensures the project administration is complete, accurate and according to the guidelines of the European Commission. There are two external experts who form the Advisory Board and advice on student training and scientific matters: Prof dr. Caroline Tapparel, Medical Faculty University of Geneva, and Prof dr. Paul Britton, The Pirbright Institute Compton UK.

Within HONOURs there will be high quality training with specific HONOURs courses:

• VIDISCA-NGS (Academic Medical Center, the Netherlands).
• Advanced VIDISCA-NGS (Academic Medical Center, the Netherlands).
• Nonhuman primates in biomedical research (Biomedical Primate Research Centre, the Netherlands).
• Reverse genetics (Institute for Virology and Immunology, Switzerland).
• Virus-host interactions on airway epithelia (Institute for Virology and Immunology, Switzerland).
• Infectious Diseases (Academic Medical Center, the Netherlands).
• Random priming-NGS (Katholieke Universiteit of Leuven, Belgium).
• Direct next generation sequencing (Friedrich Loeffler Institute, Germany).
• Novel diagnostics (University of Leeds, UK).
• Metagenomics and microarrays for virus detection (Friedrich Loeffler Institute, Germany).
• High throughput nested RT-PCR and degenerative oligonucleotide design (Charité - Universitätsmedizin Berlin).
• Protein production (INGENASA, Spain).
• Flavivirus Serology (Universität Bern).
• High throughput analysis of ticks and mosquitoes by pan-virus family and real-time RT-PCR (Labor Spiez, Switzerland).