Project description
mRNA vaccine technology for asthma
Asthma is caused by excessive immune responses to harmless environmental allergens and affects hundreds of millions of people worldwide. Despite their role in immune tolerance, dendritic cells fail to suppress these responses in asthmatic airways, leading to chronic inflammation. Emerging evidence suggests that lipid nanoparticles, the delivery vehicles used in mRNA vaccines, can induce immune tolerance rather than activation under certain conditions. With the support of the Marie Skłodowska-Curie Actions programme, the mRNAsthma project investigates whether this tolerogenic property can be harnessed in the lung to prevent asthmatic responses. Researchers will characterise dendritic cell and T cell responses to mRNA vaccines in airway tissue and test whether this approach can protect against allergen-induced asthma in preclinical models.
Objective
Dendritic cells (DCs) are antigen presenting cells that promote immunity to pathogens, as well as tolerance to innocuous antigens, and are therefore critical regulators of both immunity and immune homeostasis. However, during asthma this ability to promote peripheral tolerance is dysregulated, leading to the formation of inappropriate TH2 responses to harmless antigens, and allergic inflammation in the airway. Peripheral tolerance has been postulated to be promoted by DCs undergoing homeostatic maturation, a process by which DCs become activated, migrate, and gain the ability to present antigen in the absence of inflammatory stimuli.
Recent data from my host laboratory has shown that DCs exposed to unadjuvanted lipid nanoparticles (LNP) undergo homeostatic maturation, mimicking the response DCs mount to apoptotic bodies. In addition, unadjuvanted LNPs containing peptide cargo lead to reduced T cell responses mounted to these specific peptides, suggesting that LNPs can promote peripheral tolerance. LNP vaccines containing purified mRNA free of dsRNA contaminants also can be rendered non-immunogenic. mRNAsthma aims to adapt this phenomenon to the lung tissue microenvironment, by which DC and T cell responses to mRNA vaccines will be characterised at steady-state and during airway inflammation. In a subsequent step, we will assess if we can exploit this approach to protect from HDM-induced asthma. mRNAsthma also has an ambitious CITEseq experiment, to generate mechanistic insight of the interactions between cDC and T cells in the lung.
mRNAsthma represents an important step in my research career, to increase my skillset and learn from leaders in my field. I will use this project to advance my skills in bioinformatic analysis, as well as my skills in leadership, mentorship and science communication. mRNAsthma is therefore an ambitious project of significant translational potential, with mechanistic understanding of tolerance by cDCs central to its success.
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 biochemistry biomolecules
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- engineering and technology nanotechnology nano-materials
- medical and health sciences basic medicine physiology homeostasis
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-PF
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9052 ZWIJNAARDE - GENT
Belgium
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