| Project Detail |
Emerging infectious diseases are occurring at increasing frequency in Europe and other regions of the world, having profound impacts on public and/or veterinary health as well as disruptive effects on sector, regional or even global economy. The predominantly zoonotic nature of emerging pathogens calls for a One Health approach uniting the human medical and veterinary fields, dedicated to swiftly controlling upon emergence pathogens both at the source and in the human population. In this project, human and veterinary medical institutions, governmental regulatory agencies, expert academic groups and industrial partners, building on existing EU-funded consortia and initiatives, collaborate in establishing a universal platform for the rapid characterization, design and surge production of vaccines and neutralizing reagents against known as well as novel emerging pathogens, in particular viruses. This platform aims at ensuring a fast track for the development, registration and implementation of innovative control tools immediately after severe outbreak events are detected.
The platform will include the identification and characterization of key protective immunogens and corresponding neutralizing antibodies, based on both in silico and in vitro studies, and supported by in vivo studies that have or will generate knowledge on the pathogenesis and immune-kinetics of ZAPI target viruses in model and target animal species. These animal models will be used to characterize protective or therapeutic efficacy of developed vaccines and neutralizing reagents. In silico B-cell epitope mapping and state-of-the-art immune-structural analyses will further predict key immunogens of target as well as related viruses, and demonstrate potential of immuno-profiling technologies to be applied in the face of emerging virus outbreaks. Multi-specific antibody libraries will be constructed based on the swift generation of a broad range of conventional murine monoclonal antibodies as well as completely defined genetically-engineered humanized antibodies and nanobodies. High Throughput Sequencing assays will be developed to efficiently characterize the neutralization capacity of these antibodies within the framework of an automated workflow. Upon an incursion of a novel virus, tailor-made HTS assays will be developed to screen the established antibody libraries for virus neutralizing activity, and to identify B cells from infected individuals, that produce neutralizing antibodies. In both cases, the sequences of these antibodies will be determined to develop recombinant antibodies using systems suitable for rapid, large-scale production. The most promising and potent immunogens and neutralizing reagents will be fed into a universal platform, independent of mammalian cell cultures, for rapid and high-yield production.
Because a unique expression and production system leading to vaccine and/or neutralizing reagent production is unlikely to be successful for the full range of newly emerging viruses in the future, it is essential to develop a universal platform relying on complementary expression and production systems, to be used according to a built-in decision-tree. We therefore include several options within the development pipeline to avoid shortcomings associated with a particular expression or production system. Key immunogens will be either expressed as purified subunits preferably in prokaryotic, fungal or insect cells, or be expressed from the genome of DNA-launched RNA virus replicons. Their immunogenicity will be screened in small-animal models. Selected candidates will further be tested for immunogenicity and efficacy in small animal models and target animal species. At least two expression systems will be validated at medium production scale. Classical benchmark vaccines, produced by existing mammalian or avian cell-based systems, will be used as positive controls in vaccination-challenge experiments. Key neutralizing antibodies will be engin |
