Project description
Glycans, functional virus receptors and novel antiviral vaccines
Current assays fail to determine the receptor specificity and vaccine efficiency of the influenza A virus, as they do not represent receptors of the human upper respiratory tract. The lack of these receptors in laboratory hosts during vaccine production significantly decreases yields, resulting in vaccine mismatch that increases antigenic drift. The objective of the EU-funded Sugar-Enable project is to elucidate the functional receptor of human influenza A viruses. Researchers will investigate how glycan specificity changes due to immune pressure, attempting to identify the glycan that is utilised by all human influenza A viruses. With this knowledge, better surveillance techniques, culture models and structure-based inhibitors can be developed. Ultimately, the project will enable new possibilities for creation of the glycan-analogue inhibitors and the better vaccines.
Objective
Our current assays to determine the receptor specificity and vaccine efficiency of influenza A virus fail as they do not represent receptors available in the human upper respiratory tract. The lack of these receptors in our laboratory hosts to create vaccines significantly dampen yields, the resulting mismatched vaccines do not afford proper protection and further drive antigenic drift.
The objective of this proposal is to elucidate the functional receptor of human influenza A viruses. By using antigenically drifted viruses, we expect to understand how glycan specificity changes due to immune pressure but it will also lead to the identification of a glycan that is utilized by all human IAV viruses. With this knowledge, better surveillance techniques, culture models and structure-based inhibitors can be developed. Using a novel and sophisticated cell-engineering tool, based on lipidated sugars, we will show functional glycan receptor usage. In addition, I will create cell lines in which human influenza A vaccine viruses grow to high titers without adaptation, thus providing superior protection.
To achieve this goal, I propose to enzymatically synthesize complex glycans (AIM 1), including sialic acid modifications that are found on the respiratory tract epithelial cells of humans and other IAV hosts. Several enzymatic methods and glycan array tools are in place, and thus the chance of success is high. I already set-up preliminary methods for the use of lipidated N-glycan structures and extensive knowledge on SEEL is present in the department (AIM 2). For creating super vaccine producing cell lines I will use genetic approaches that previously have shown to be successful (AIM3).
The systems dealing with sugars enabling function, either for infection or vaccine research, I term sugar-enable, will provide new endeavors to create glycan-analog inhibitors and will bring us steps closer to better vaccines.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences health sciences infectious diseases RNA viruses influenza
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences biochemistry biomolecules carbohydrates
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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)
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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
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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-STG - Starting Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-STG
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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.
3584 CS Utrecht
Netherlands
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