Glyco-protein arrays for functional virus surveillance

Projektinformationen

arrayed surveillance

ID Finanzhilfevereinbarung: 101183378

DOI

10.3030/101183378

Projekt abgeschlossen

EK-Unterschriftsdatum 30 Juli 2024

Startdatum 1 August 2024

Enddatum 31 Januar 2026

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

UNIVERSITEIT UTRECHT
Netherlands

Periodic Reporting for period 1 - arrayed surveillance (Glyco-protein arrays for functional virus surveillance)

Berichtszeitraum: 2024-08-01 bis 2026-01-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The objective of this ERC PoC project is to establish the technical and commercial feasibility of our recently developed glycan-arrays in which we determined the minimal receptor for duck, chicken, and human influenza A viruses respectively. We also determined structures that are vital for viruses as intermediate receptors on the avian-mammalian interface. With our experience in printing arrays, we now want to add proteinaceous receptors for coronaviruses as well. This mixed “glyco-protein” array will then be employed for functional surveillance of two virus families with significant pandemic threat. The ERC program “sugar-enable” has developed different glycan arrays that should be employed in the real world to detect potential pandemic viruses as soon as possible, now making a huge societal impact. In this project, we aim to conduct a technical and commercial feasibility study:

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

While the original work plan focused on the technical and commercial validation of glyco-protein arrays for functional virus surveillance, part of the project effort was strategically redirected. This was driven by the emergence of novel reassortant H5N1 viruses in Cambodia, combining clades 2.3.2.1 and 2.3.4.4 alongside antigenically drifted H5 variants. These viruses, which showed high pathogenicity in humans (fatality rates up to ~70%) and continued circulation in live bird markets and backyard poultry, represent a significant pandemic threat. To address this, a PhD student was recruited to study these viruses in detail, generating critical biological insight and materials directly relevant to the functional surveillance objectives of the project. This work provides essential input for understanding receptor binding and antigenic variation in currently circulating high-risk strains—key parameters that the glyco-protein array platform is designed to assess. As a result of this strategic shift, some originally planned technical deliverables, particularly related to prototype field validation and scanner integration, were only partially achieved within the project period. However, the generated data and virus panels significantly strengthen the scientific and practical foundation for future implementation of the array technology in real-world surveillance settings.

the project has reached both industrial stakeholders and key technology providers. In particular, we have maintained and further strengthened our collaboration with Innopsys, a leading developer of fluorescence slide scanning technologies. As part of our ongoing efforts to improve and validate array readouts, we acquired and implemented the InnoQuant fluorescence slide scanner platform in our laboratory. This system enables high-resolution, quantitative, and multiplexed fluorescence imaging, including simultaneous multi-channel detection, which is essential for scaling up glyco-protein array analysis. The integration of this technology has allowed us to further optimize detection strategies, assess multiplexing capabilities, and improve reproducibility of array-based measurements. Importantly, this represents a concrete step toward translating the array platform into a robust and scalable tool, aligned with industrial standards and workflows. Beyond technology uptake, this interaction provides a pathway for future co-development of optimized detection systems and potential deployment of array-based surveillance tools in field-compatible formats.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

During the project, we generated two major scientific outputs that directly support the concept of functional surveillance. First, we characterized the phenotypic properties of recently emerged reassortant H5N1 viruses from Cambodia, combining clades 2.3.2.1 and 2.3.4.4. These viruses showed altered receptor binding properties and continued circulation in high-risk interfaces such as live bird markets. Second, we identified molecular markers associated with human-type receptor specificity in H5 hemagglutinin. These markers provide mechanistic insight into zoonotic potential and represent measurable features that can be integrated into functional assays. Together, these results address a central gap in current surveillance approaches: the lack of direct linkage between viral genotype and phenotype. By defining phenotypic signatures and their molecular determinants, this work strengthens the scientific basis for implementing glyco-protein arrays as tools for real-time functional risk assessment.