Titel Promotor Affiliaties "Korte inhoud" "Next generation HIV-1 immunogens inducing broadly reactive neutralising antibodies" "Guido Vanham" Virologie "GeneralWe start from the hypothesis that in HIV-1 infected individuals with HIV-1 specific broadly neutralising activity in serum, virus variants with specific envelope characteristics are present that have elicited these responses and that could elicit these responses again as a vaccine immunogen. Our goal is to gather the skills and efforts of several active research groups in trying to achieve new HIV-1 immunogens, ranging from clinical samples to small animal models.SpecificCloning and sequencing HIV-Env genes, and development of a genetic and functional (sensitive to antibodies) env database.High-throughput cloning, expression and purification of HIV env genes that in potential may elicit broadly Nabs and the creation of Env protein arrays.Antigen optimisation and identification of novel neutralisation-sensitive epitopes as HIV-1 vaccine candidates.Rational mutagenesis of env aimed at de-protecting highly conserved neutralisation epitopes that are kept in a cryptic conformation or at stabilising env in a conformation that optimally presents the CD4-binding site.Novel strategies for inducing inter-clade and intra-clade cross-reactive responses.Optimisation of antigen targeting to the correct cells of the immune system.Novel adjuvants for Th2 response and delivery strategies for mucosal routes.Optimisation of immunisation routes and prime-boost schedules.Exploitation of the knowledge on the mechanisms of HIV mucosal infection and mucosal immunity for the development of safe and effective vaccines capable of preventing HIV-1 infection.Development of an immunological platform with standardised procedures." "Inter- en intracommunautaire dynamiek van SARS-CoV-2- verspreiding door een combinatie van sequentiebepaling van het viraal genoom en fylodynamische analyse" "Piet Maes" "Laboratorium Klinische en Epidemiologische Virologie (Rega Instituut), Université Libre de Bruxelles, Universiteit Gent" "Sinds de introductie van SARS-CoV-2, verspreidt het virus zich zeersnel en heeft het wereldwijd ernstige respiratoire pathologie veroorzaakt. Het virus is afkomstig van een zoönotische overdracht van dier naar mens, waarbij waarschijnlijk een vleermuis of zelfs een schubdier het virus droeg en een mens infecteerde. Dit betekent dat het virus zich nog steeds aanpast aan zijn nieuwe gastheer, de mens. Dit wordt bijvoorbeeld geïllustreerd door een nog steeds suboptimale binding tussen de menselijke ACE2-receptor en het receptorbindende domein van het virale spike-eiwit. Deze evolutionaire druk veroorzaakt mutaties waardoor we de evolutie van het virus op de voet kunnen volgen. Onze onderzoeksvraag in ditprojectvoorstel is hoe dit nieuwe coronavirus zich verspreidt onder de bevolking zowel op 'microniveau' (bijvoorbeeld in een school of hospitaal) als op 'macroniveau' (landelijk). We stellen voor om de ruimtelijke distributie van Belgische SARS-CoV-2-clusters te bestuderen door een combinatie van volledige sequentiebepaling en phylodynamische analyse. Dit om te beoordelen hoe de spatiotemporele distributie van deze clusters evolueerde van de lockdown tot de afgelopen zomerperiode. Bovendien willen we nieuwe positieve gevallen onderzoeken gedurende de komende 12 maanden in een bijna 'real-time' manier om de evolutie van de circulatiedynamiek door de tijd te beschrijven en de impact van COVID19-metingen op ruimtelijke transmissie in de tijd tebeoordelen. " "CARE Corona Versnelde R&D in Europa" "Johan Neyts" "Laboratorium Virologie en Chemotherapie (Rega Instituut), Klinische Farmacologie en Farmacotherapie" "The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has emerged as the largest global health threat to humanity in this century. According to the World Health Organisation Situation Report of March 28th 2020, 571,659 patients were  diagnosed with Coronavirus Disease 2019 (COVID-19) and 26,493 deaths were reported globally. The wide spectrum of clinical symptoms, disease severity in high risk individuals, transmission efficiency and high mortality, raises an immediate need for vaccines or therapeutics. Given that the viral variant is new in the human population and emerged less than 4 months ago, there is no vaccine or approved therapies. The Corona Accelerated R&D in Europe (CARE) consortium is a coalition of 37 globally renowned academic institutions, pharmaceutical companies and non-profit research organizations who have committed to rapidly and efficiently address this emergent health threat, and the main objectives are: the development of therapeutics (i) to provide an emergency response towards the current COVID-19 pandemic by drug repositioning and (ii) to address the current and/or future coronavirus outbreaks by broad-spectrum small-molecule drug discovery and/or virus-neutralizing antibody discovery. To achieve this, a collection of repurposed drugs, focused libraries and small molecule libraries will be screened against SARS-CoV-2, other emerging SARS-CoV-2 clades and related coronavirus genera in phenotypic or target-based assays. A focused medicinal chemistry campaign will identify small-molecule hits, and Absorption, Distribution, Metabolism and Excretion (ADME), pharmacokinetic/pharmacodynamic (PK/PD), potency and safety of these therapeutic candidates will be assessed in vitro and in animal models. Virus-neutralizing monoclonal antibodies will be generated and further characterized. Immune markers will be identified contributing to the host immune responses to SARS-CoV-2 infections, and the correlation with clinical and virological outcomes will be determined. Finally, lead candidates will be advanced into Phase1 and Phase 2 clinical trials in humans. With this reactive response, the CARE consortium is dedicated to win the fight against coronavirus" "Validation study of the open ADAMTS13 conformation assay as a novel biomarker for correct diagnosis and predicting relapse in immune mediated thrombotic thrombocytopenic purpura" "Karen Vanhoorelbeke" "Chemie, Campus Kulak Kortrijk" "Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing antibodies against the blood protease ADAMTS13. In the current guidelines, the diagnosis of iTTP is established by an ADAMTS13 activity below 10% and presence of anti-ADAMTS13 autoantibodies. While both two biomarkers have proven very useful in TTP diagnosis, there are still seronegative gaps in TTP diagnosis. We recently discovered that ADAMTS13 with an open conformation, open ADAMTS13, is a novel biomarker for iTTP. However, it has not been well elucidated if open ADAMTS13 analysis would (1) improve iTTP diagnosis correctly and (2) be an integrated tool for predicting relapse in iTTP patients. In this project, we are planning to validate the efficacy of open ADAMTS13 analysis as a novel biomarker for correct diagnosis and predicting relapse in iTTP. Sufficient iTTP plasma samples will be available via international collaborations and via my unique Japanese TTP cohort." "Het VyCAP platform voor de isolatie en hoogwaardige analyse van individuele cellen" "Paul Declerck" "Mechatronica, Biostatistiek en Sensoren (MeBioS), Therapeutische en Diagnostische Antilichamen, Klinische en Diagnostische Immunologie, Laboratorium voor Ziektemechanismen in Kanker" "Deze infrastructuuraanvraag betreft de aankoop van het VyCAP platform voor de isolatie van individuele (zeldzame) cellen voor hoogwaardige RNA- en DNA-analyse of voor celcultuur toepassingen. Het platform is compatibel met alle technologieën inzake analyse van individuele cellen en ondersteunt een brede waaier aan applicaties, waaronder de analyse van circulerende tumorcellen, van het secretieprofiel van individuele cellen en de selectie van monoklonale cellijnen. De technologie verruimt de onderzoekscapaciteiten van de aanvragers voor hun lopende projecten, waaronder immuunprofilering, ontwikkeling van monoklonale antilichamen voor therapeutische en diagnostische doeleinden en het selecteren van specifieke monoklonale cellijnen, terwijl de geassocieerde kosten dalen. Daarnaast heeft de brede toepasbaarheid van het VyCAP platform tot gevolg dat het ook voor een meerwaarde zal zorgen in verschillende toekomstige onderzoeksprojecten. Verschillende onderzoeksgroepen hebben bovendien al aangegeven dat ze interesse hebben om het platform te includeren in hun (toekomstig) onderzoek." "Evaluatie van een combinatie van op immunotherapie gebaseerde therapieën om een functionele genezing van HIV-infectie (HIVACAR) te bereiken" "Karine Breckpot, Kris Thielemans" "Laboratorium voor Moleculaire en Cellulaire Therapie, Basis (bio)-medische wetenschappen, Fysiologie" "The main goal of HIVACAR proposal is to change the current paradigm of HIV treatment by obtaining a functional cure for HIV (i.e., control of viral load to levels below the threshold of 50 copies/ml and maintenance of high CD4+ T-cell count after discontinuation of antiretroviral therapy) thanks to effectively targeting residual virus replication and viral reservoirs. In order to do so, the planned novel strategy is to successfully combine immune-based therapies, including therapeutic vaccines and broadly neutralizing antibodies with latency reversing agents, in a proof-of-concept phase IIa clinical trial. HIVACAR project will lead to a reduction of the actual costs related to HIV treatment and management and of the social public health as well as an improvement in the patients’ quality of life. HIVACAR project has been conceived under the framework of responsible research and innovation, so patients and other stakeholders will have a key role from the inception of the project until obtaining the results. Patients will be perfectly aware of how this therapy has been conceived and the real impact and change in their actual quality of life, as well as how the clinical trial has been designed and the consequences of participating in it. In addition, patients (and the general population) will tailor the project and its results dissemination and communication. This patient engagement will not be limited to the clinical trial but also to the rest of the activities of the project, so patients and the general society will be aware of how the research is developed and can include the patients’ point of view in the research activities. In addition, the socio-economic and psycho-social impact of the new treatment will be also analysed so overwhelming data on the benefits and impact of the new treatment will be obtained and shown to all the stakeholders."