Project description
Beyond neutralisation: a new function of therapeutic antibodies against respiratory infections
Respiratory infections are the leading cause of death from transmissible diseases. The emergence of new pathogens, the spread of antimicrobial resistance and recurring seasonal epidemics underscore the urgent need for innovative treatments. Although therapeutic antibodies can be highly effective, their protective effects are often short-term. Supported by the Marie Skłodowska-Curie Actions programme, the TI-LAB project is investigating a new function of therapeutic antibodies to enhance innate immune defenses against respiratory infections. The TI-LAB project will examine how innate immune cells respond to antibody–pathogen immune complexes and how this relates to memory-like responses. The findings are expected to provide new insights into achieving sustained protection against respiratory infections through therapeutic antibodies.
Objective
Therapeutic antibodies (Abs), have become crucial drugs in modern medicine, showing success in treating various diseases, including the global COVID-19 pandemic. Although anti-infective Abs are usually administered parenterally, recent findings demonstrated that local administration into the respiratory tract of an Ab neutralizing Pseudomonas aeruginosa (Pa) not only blocks primary infection but also offers prolonged protection against secondary infections. However, the molecular mechanisms supporting the immunomodulatory features of the Ab and establishment of long-lasting protection remain unknown. Preliminary data from the host laboratory indicate that murine macrophages primed with Ab+Pa immune complexes (ICs) display an antimicrobial pro-inflammatory phenotype, further enhanced after exposure to Toll-like receptor ligands, suggesting the induction of immune memory. This capacity termed trained immunity (TI) depicts a type of immune memory within innate immune cells that recall previous epigenetically-encoded information under heterologous stimulation. Using a combination of molecular, metabolic, and epigenetic approaches in conjunction with omics-based techniques, TI-LAB (Trained immunity Induced in the Lungs by therapeutic AntiBodies) will define the capacity of ICs to induce TI. Furthermore, TI-LAB will provide a detailed analysis of the intracellular signaling pathways involved in IC-mediated TI. Finally, the protective effects of IC-mediated TI will be assessed using an in vivo model of respiratory infection. This proof of concept will be extended to other respiratory pathogens to determine if TI induced by ICs is a conserved mechanism across pathogens. Overall, our findings will reveal a new function of anti-infective Abs in immune memory and reprogramming of the innate immune system, which should help design new treatments against respiratory pathogens.
Fields of science (EuroSciVoc)
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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.
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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)
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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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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-2024-PF-01
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75654 Paris
France
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