Project description DEENESFRITPL 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. Show the project objective Hide the project objective 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 natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenzamedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesnatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-STG - ERC Starting Grant Call for proposal ERC-2018-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator UNIVERSITEIT UTRECHT Net EU contribution € 1 441 681,00 Address Heidelberglaan 8 3584 CS Utrecht Netherlands See on map Region West-Nederland Utrecht Utrecht Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITEIT UTRECHT Netherlands Net EU contribution € 1 441 681,00 Address Heidelberglaan 8 3584 CS Utrecht See on map Region West-Nederland Utrecht Utrecht Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
