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Utrecht University

Country: Netherlands

Utrecht University

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815 Projects, page 1 of 163
  • Funder: EC Project Code: 749719
    Overall Budget: 177,599 EURFunder Contribution: 177,599 EUR

    New vaccine modalities need to be developed that can activate more potently the immune system, in this regard, adjuvants augment adaptive immune responses and can improve vaccine performance. Aluminium salt (alum) is the most commonly used adjuvant for human vaccination. However, it drives primarily TH2-effector responses and is not effective for vaccines that target mucosal surfaces. Thus, safe and potent adjuvants need to be developed that can increase and direct vaccine-specific immunity. Recent advances in our understanding of innate immune responses are providing opportunities to design better adjuvants. The innate immune system senses microbes through pattern-recognition receptors (PPRs), which include the Toll-like receptors (TLRs), and intracellular NOD-like receptors (NLRs) and C-type lectin-like (CTLs) receptors that are expressed by immune cells. Activation of these receptors leads to the production of cytokines that provide early defences during infection. Cytokines also regulate adaptive immunity by controlling the quantity and quality of B and T cell activation, which in turn results in protective immune responses to pathogens. Pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipopeptides, and peptidoglycan fragments can activate PPRs and are attractive compounds for the development of new adjuvant. Although during microbial infection many different PRRs are activated, almost all adjuvants that are being developed rely on the stimulation of a single PRR. In this project, we propose that compound adjuvants derived by the covalent linking of two PAMPs (fusion PAMPs), for example, TLR2 and NOD agonists, will ensure that immune cells are being exposed to both, resulting in efficient cross talk of signal transduction pathways and in synergistic immune activation. If so, chimeric immune modulators (fusion PAMPs) can be employed at lower adjuvant concentrations, thereby minimizing unwanted side effects.

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  • Funder: EC Project Code: 749996
    Overall Budget: 177,599 EURFunder Contribution: 177,599 EUR

    Influenza A virus has two major envelope glycoproteins: HA and neuraminidase (NA). HA binds to sialic acid moieties of glycoconjugates of the host respiratory cells to initiate infection, whereas NA facilitates the release of progeny viruses from infected cells by cleaving sialosides. It is well documented that binding preference is a major determinant of influenza virus host range and avian viruses preferentially bind Neu5Acα(2,3)Gal, whereas human viruses bind Neu5Acα(2,6)Gal. This difference in specificity represents a barrier for transmission of avian viruses into humans. Glycan arrays have been used to assess influenza A virus receptor specificity. However, the currently available glycan arrays contain only a fraction of the glycans found on human airway epithelial cells and cannot uncover glycan binding specificities. Thus, we propose to develop an array that contains glycans representative of the structures found in human airways, since it is a priority in order to understand the biology of influenza virus transmission and pathogenesis. In addition, it has been described that there are two pathways by which influenza virus enters cells. It is believed that some N-glycans serve as attachment factors for concentrating virus particles on the surface of the host cells. However, only specific cell surface proteins modified by appropriate N-glycans can facilitate cell entry. The elucidation of the influenza virus receptor structure will unveil the mechanism at molecular level by which virus enters the cell. To this end, we will develop an experiment, which allows us to identify glycoprotein receptors of flu virus using cell surface glycan editing. The full comprehension of multi-branched glycans, along with the identification of the glycoproteins receptors of influenza virus, will allow the development of new and more efficient glycan-based therapeutics.

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  • Funder: EC Project Code: 306390
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  • Funder: EC Project Code: 339647
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  • Funder: EC Project Code: 101041824
    Overall Budget: 1,500,000 EURFunder Contribution: 1,500,000 EUR

    Human ads are Internet influencers who earn revenue by creating and monetizing authentic and relatable advertising content for their armies of followers, by relying on business models such as influencer and affiliate marketing. This content often results not only in commercial but also political (hidden) ads, which look the same, are posted by the same persons, are displayed in the same digital space, to the same audiences, and raise the same transparency issues. In this environment, consumers and citizens can no longer distinguish between ads and non-ads, and between commercial and political communications. They are faced with a double transparency problem: (i) human ads have incentives to hide commercial interests, and (ii) platforms have incentives to algorithmically amplify human ads engagement in opaque ways. This reflects a general good faith and fair dealing problem: the social media economy is increasingly based on deceit, which leads to new forms of vulnerability for consumers and citizens on digital markets. Given its complexity and relative novelty, this phenomenon has not yet been the object of sustained academic or regulatory inquiry. HUMANads tackles this comprehensive research gap by exploring why a general European legal regime on fair advertising by human ads on social media platforms is necessary, and what it would entail. First, it articulates new theory of fair advertising in EU consumer law, in the context of content monetization by human ads across commercial and political speech. Second, it gathers evidence relating to business models, advertising prevalence and legal uncertainty through innovative interdisciplinary methods including digital ethnography, comparative law and natural language processing (NLP). Third, it proposes criteria for the assessment of resulting consumer harms, and translates them into a new normative governance model mandating more stringent transparency obligations on social media platforms.

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