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Control and triggers of afucosylated IgG responses.

Prof G. Vidarsson

Duration:

Name researcher:

4 years

Amount granted:

€ 449.900

Year:

2024

Project number:

2412

Antibodies can be formed after blood transfusion, and in pregnancy, causing life threatening complications. Surprisingly, some antibodies are relatively harmless, with magnitude not corresponding to enhanced pathologies. We have recently discovered a unique mechanism resulting in altered antibodies with elevated functional properties due to altered sugars in the antibodies. Our findings show this is mimicking responses we generate against certain viral infection (e.g. HIV and COVID-19) and in malaria. Here we plan to investigate how these responses are initiated, so that we can prevent this in the future from occurring after transfusion or in pregnancy. Alternatively, same information can be used to generate rational approached to activate this mechanism to induce better protective immune responses. This proposed research project aims to make blood transfusions safer by allowing us prevent and/or to identify patients at risk of complications, but also providing a sound basis for improving vaccines against difficult targets, including SARS-CoV-2, HIV, and malaria. In step 2, we will create a cell system for testing these new APS CAR T cells. For this we will copy information from disease cells from APS patients and transfer that into laboratory cells. With these, we can show the CAR T cells cure the copied diseased APS cells in the laboratory. In step 3, we expand the experiments to actual APS patient cells to test how well these APS CAR T cells work. The results could be the initial steps towards a radically improved treatment of APS.

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