Work Packages

Infectious outbreaks in animals and humans emerge unexpectedly, illustrated by the recent outbreak of Ebola in West Africa. The causative agent of an outbreak can be new, caused by a yet undiscovered pathogen, or caused by a known but unexpected pathogen. History has shown that the spread of an animal virus to humans (zoonosis) is the main source of novel infections in humans, and preparedness for zoonoses is required. Currently there is no all-round training of researchers in infectious outbreaks and zoonoses, therefore the main objective of this Marie Curie ITN is to train young researchers on all aspects, separated into 5 Work Packages on emerging viral infections.

An Outbreak Antenna Work Package (WP2) will cover diagnostics in both the veterinary and the human health sector. Unexpected or novel agents have to be identified, which will be covered by the Pathogen Identification Work Package (WP3). The Virus Culture and Animal Models Work Package (WP4) will culture virus in sophisticated ex-vivo cell cultures, if needed via reverse genetics, to supply pure virus stocks, animal models to be inoculated by the virus stock, and candidate vaccines. Aim is to fulfil the Koch’s postulates and the production/challenge with candidate vaccines, and/or antivirals. The Advanced Diagnostic Work Package (WP5) will design and make novel diagnostics available to identify the new or unexpected agents and the Awareness Work Package (WP6) will perform training to communicate with the relevant stakeholders.

As long as there is no outbreak to focus on, each ESR will work on an independent, individual research project fitting to one Work Package and on the side be part of other WPs to ascertain all-round outbreak management training and expertise building.

 

+Work Package 1. Ethics Requirements

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.

+Work Package 2. Outbreak Antenna

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 9 ESRs, guided by 6 senior scientists. The team will monitor whether there are suspicions of new entries, or unexpected infections in their fields. At 6 sites the Outbreak Antenna will be operational: 3 sites to identify outbreaks in animals (Friedrich Loeffler Institute, Germany, Institute for Virology and Immunology, Switzerland, MSD Animal Health, the Netherlands) and 3 hospital sites to identify outbreaks in humans (Academic Medical Center, the Netherlands, University of Leuven, Belgium, Labor Spiez, Switzerland).

+Work Package 3. Pathogen Discovery

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.

+Work Package 4. Virus Culture, Reverse Genetics, and Animal Models

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.

+Work Package 5. Advanced Diagnostics

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.

+Work Package 6. Awareness

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.

+Work Package 7. Consortium Management and Assessment of Progress and Results

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.

+Work Package 8. Training

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 (Universitäts Klinikum Bonn, Germany).
  • Protein production (INGENASA, Spain).
  • Flavivirus Serology (Labor Spiez, Switzerland).
  • High throughput analysis of ticks and mosquitoes by pan-virus family and real-time RT-PCR (Labor Spiez, Switzerland).

HONOURs

Host switching pathogens, infectious outbreaks and zoonosis; a Marie Sklodowska-Curie Innovative Training Network.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 721367.