Project description
A unique model system shines light on flu virus evolution
Seasonal influenza is highly infectious. Global pandemics occurred thrice in the twenty-first century alone. Vaccines can effectively prevent respiratory infection but the genes that code for influenza surface proteins (antigens) can change. These 'new' viruses often evade the human immune response and novel vaccines are required for these novel viral strains. Prolonged infection may also contribute to virus evolution. NaviFlu is investigating this hypothesis in a novel culture system mimicking the human airway epithelium. It will provide a unique opportunity to manipulate and study long-term influenza infection, hopefully leading to the amelioration of a significant threat to public health worldwide.
Objective
Seasonal influenza viruses re-infect us repeatedly, escaping antibody recognition, due to the evolution of the virus itself. Being able to predict when and how the virus will evolve would be transformative for influenza virus control. Problematically, we have only observed one of the likely many possible routes of virus evolution. We do not know how many viable routes may have existed or about the repeatability of the observed evolution. These knowledge gaps limit the predictability of influenza virus evolution. NaviFlu will fill these gaps by rigorously assessing the repeatability of influenza virus evolution and the diversity of routes the virus can explore.
Recent work has shown that prolonged influenza virus infections can result in substantial virus evolution and occasionally portend virus mutational patterns on a global scale. However, observing large numbers of such infections is challenging. We will use an innovative ex-vivo human airway epithelium culture system to artificially create and study prolonged human infections. Together with cutting-edge next generation sequencing and new analysis tools, we will quantify the evolutionary landscape of seasonal influenza viruses.
The project has three objectives, each building in complexity:
1–Quantify the evolutionary dynamics of seasonal influenza viruses in the absence of antibody-mediated selection.
2–Determine how the antibody complexity of immune sera shape the evolutionary trajectories of virus antigenic evolution.
3–Quantify the impact of differences in selection pressures by site of infection and underlying host variation on virus evolution.
Through these objectives we will “play evolution forwards”, revealing the relative roles of different factors governing the mode and tempo of influenza virus evolution and quantify the predictability of virus evolution. This will improve the design of influenza vaccines, enhance prospects for influenza control, and lay new groundwork for exploring virus evolution.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1081 HV Amsterdam
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.