Translink Work Plan

  • Clinical data, biobanking and statistical analysis
    This WP will be responsible for the smooth running of the clinical study. In particular, it will make sure that TRANSLINK enrolls in the 3 centers the cohort of approximately 2600 BHV recipients necessary for the 2 arm study (transactional and prospective). It will also ensure close patient monitoring and will be responsible for samples shipment to the TRANSLINK reference laboratories in WP2 and WP3 but also to a Partner in WP5 that will be involved in the design of novel compounds able to neutralize anti- BHV antibodies. Finally, it will be in charge of the statistical analyses of the project.
  • Biochemical characterization of engineered BHV and analysis of the anti-BHV humoral immune response
    The objective will be to undertake, coordinate and centralize:

-the in vitro assessments to identify the carbohydrate moieties on glycosphingolipid, glycopeptide and recombinant mucins on porcine/bovine BHV potentially exposed to BHV recipients and

-the study of the humoral immune response of the patients recruited by WP1, BHV-recipients or not. Emphasis will be put on the anti anti-Neu5Gc, anti-_Gal antibodies and hyaluronan immune responses, both quantitatively and qualitatively (arrays patterns)

  • Mechanisms of BHV damage and possible recipient disease mediated by anti BHV immune response
    The exploration of the immune mechanisms responsible for BHV deterioration as well as possible undesirable effects in BHV recipients (vascular inflammation) will be performed. In this regard, a special focus will be devoted to the natural immune response to BHV, as previous studies have shown that heterophilic antibodies, particularly anti-_Gal (whose titres are expected to rise following BHV implantation) may ”paradoxically” enhance bacterial infection, a common event after BHV implantation.

-    Potential infectious risk related to the anti-BHV immune response
This WP will shed insight into the mechanisms that may increase susceptibility to infection in BHV recipients. At this stage, however, evidence already exists that both anti-_Gal and anti non-Gal antibodies (especially anti-Neu5Gc) may lead to detrimental effects to man.

  • Remedies: prevention and treatment
    As a consequence of the knowledge achieved in the aforementioned WP and due to the cutting-edge technology of the three SMEs partner TRANSLINK will embark in a “remedy-programme” that will, either pre-emptively (by generating suitable KO-animals) or therapeutically (by using specially designed polymer), protect BHVs and possibly BHV recipients from BHV-derived side-effects detrimental to health.