Category: Centers

Karolinska Institutet participates in WP2, 5 and 6 through the participation of Marcus Buggert.

The Buggert group conducts research on cell-mediated immunity. More specifically, we are interested in understanding how memory T cells recognize and eliminate viral infections. Much of our research is focused on the CD8+ T cell arm of cell-mediated immunity. CD8+ T cells are absolutely critical for immune control of most viral infections and also represent a major cellular component of immune therapies that have entirely revolutionized cancer care.

Our group use cutting-edge bulk- and single-cell technologies, including 30-parameter flow cytometry, gene expression, RNA-seq, ATAC-seq, TCR-seq, and proteomics analysis to dissect the heterogeneity and function of memory T cell immunity. Through these platforms, we study different aspects of human memory T cell biology, with an overall aim to i) study the heterogeneity of circulating and resident memory T cells in humans, ii) identify alternative functions of memory T cells in human tissues, and iii) understand how memory T cells maintain control of viral infections.

Zealand Region participates in WP2 and WP6

The Department of Clinical Immunology, Zealand University Hospital, Køge is responsible for genetic epidemiological research with focus on HLA and risk of infections. It provides access to the Danish Blood Donor Study (DBDS) which is a nationwide ongoing prospective research cohort on blood donors. DBDS include detailled information on life style, behaviour, sleep, stress, psycological and somatic health scores both prior to and during the COVID-19 pandemic.

The South African researchers are all affiliated with the Faculty of Health Sciences, University of the Witwatersrand (Wits) (https://www.wits.ac.za/health/). The Wits Health Consortium (Pty) Ltd (WHC) is wholly-owned by Wits University and provides financial and human resources oversight for internationally funded research and clinical trials (https://www.witshealth.co.za/). The National Institute for Communicable Diseases (NICD) provides a strategic resource for laboratory investigation of infectious diseases of public health importance in South Africa but also the greater African continent (https://www.nicd.ac.za/). The Tiemessen Research Laboratory (Cell Biology), within the Centre for HIV and STIs at the NICD, has extensive experience in studying innate immunity, particularly in the context of HIV-1 infection. The research team has varied expertise across flow cytometry, virology, immunology, molecular biology and host genetics. The clinical researchers are based at Chris Hani Baragwanath Academic Hospital (CHBH), the third largest hospital in the world, which is a tertiary level academic hospital located in Soweto, Johannesburg (https://www.chrishanibaragwanathhospital.co.za/), and at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Both hospitals are affiliated with the University of the Witwatersrand and trains both undergraduate and postgraduate healthcare workers in multiple disciplines.

The Wits Health Consortium (Pty) Ltd has the infrastructure and management systems in place to provide appropriate financial and human resources oversight for internationally funded research and clinical trials. The National Institute for Communicable Diseases (NICD) provides a strategic resource for laboratory investigation of infectious diseases of public health importance in South Africa but also the greater African continent. The Institute houses several referral laboratories offering specialist laboratory testing serving surveillance and outbreak detection and management. The NICD provides routine reports and analyses, epidemic modelling, advisories, surveillance and research related to COVID-19. The Tiemessen Research Laboratory (Cell Biology), within the Centre for HIV and STIs at the NICD, has extensive experience in studying innate immunity, particularly in the context of HIV-1 infection. The research team has varied expertise across flow cytometry, virology, immunology, molecular biology and host genetics. Chris Hani Baragwanath Academic Hospital (CHBH) is a tertiary level academic hospital located in Soweto, Johannesburg, South Africa. It serves the surrounding predominantly black African population of approximately 1,8 million individuals. Many parts of Soweto rank among the poorest in Johannesburg, although individual townships tend to have a mix of wealthier and poorer residents. It remains the third largest hospital in the world, with 3 200 inpatient beds and receives referrals from surrounding areas as far as 150 km away. It is affiliated with the University of the Witwatersrand (Wits) and trains both undergraduate and postgraduate healthcare workers in multiple disciplines. The Department of Internal Medicine at Wits occupies approximately 700 of these beds. At the peaks of differing SARS-CoV-2 waves, 400 to 500 of the beds allocated to the Department of Internal Medicine were re-allocated to the care of COVID-19 patients. As inpatient numbers increase and decrease between peaks, the numbers of allocated beds follow. The COVID-19 wards remain the responsibility primarily of the Department of Internal Medicine, with assistance from other specialties when required, depending on inpatient numbers. Two of the co-PIs involved in the setup of the cohort study, which is central to the present proposal, were tasked with setting up the wards and all processes within the COVID-19 wards.

Within the National Institute for Communicable Diseases (NICD), the Tiemessen Research Laboratory (Cell Biology) leads WP7 the WHC (Cell Biology) will be responsible for coordinating with clinicians at CHBH for the recruitment of hospitalized COVID-19 patients. The clinicians involved in the study are responsible for patient care, the clinical database and analysis of clinical data. Samples are transported to the NICD, where they will be processed in the Cell Biology laboratory (Centre for HIV and STIs) and where all laboratory assays (all biomarkers, targeted DNA sequencing, genotyping assays) under Tasks 7.2 – 7.4 will be conducted, and data analysed. The whole genome RNA sequencing (single-cell and bulk neutrophils) will be done at the NICD Core Sequencing facility (Task 7.3). Human whole genome sequencing will be conducted at the SAMRC BGI Genomics Centre, Cape Town, South Africa (Task 7.4). Bioinformatics analyses of WGS are done in collaboration with the Sydney Brenner Institute for Molecular Biosciences (SBIMB), University of the Witwatersrand. WHC will be responsible for the financial oversight for studies conducted under WP7 in South Africa. WHC will collaborate with other WP participants –  will ensure shipment of samples for viral/immunological analyses, sharing of data generated on WP7, analysis of integrated data and publication/dissemination of findings.

CNIO leads WP2 of REACT through the participation of Dr. Eva Ortega-Paíno, Scientific Director of CNIO Biobank.

To provide effective and personalized healthcare, high quality human biological samples are needed to advance in the biomedical knowledge. The CNIO Biobank is a service platform that provides the scientific community with access to human body specimens, and associated clinical information, necessary to foster patient-sensitive research, increasing biomedical awareness and promoting the development of new techniques and biomarkers.  All this allows the strategic development of research institutions and centres, respecting at all times the legal and ethical precepts, with a special focus on protecting the rights of donors.

CNIO Biobank has historically played a crucial role in the harmonisation of the Spanish biobank landscape, working with the regulatory agents and government officials for creating a common framework for the management of human samples for research, hence encouraging collaboration. In this line,CNIO biobank coordinated the first network of tumour banks at European level,and the national network of Biobanks, promoted by the Carlos III Institute of Health (2009-2017). Currently, it coordinates the Biobank Hub, within the ISCiii Biobanks and Biomodels Platform; and its Scientific Director, Eva Ortega-Paíno, is the Spain National Node’s Scientific Coordinator at the European biobank infrastructure (BBMRI-ERIC).

The Biobank unit is integrated at the CNIO, a Spanish public institution dedicated to the research, diagnosis and treatment of cancer, and affiliated to the Carlos III Institute of Health (Ministry of Science, Innovation and Universities). It is one of the 10 leading cancer research centres in the world (Scimago Institutions Rankings World Report; Nature Index) and covers the entire R&D and Innovation spectrum, from basic research to the clinic, with a view to transferring the results quickly and efficiently to the National Health System and to the pharmaceutical and biotechnology market.

IBEC coordinates WP8 and WP10 of REACT through the participation of Dr. Nuria Montserrat, lead of the laboratory “Pluripotency for Organ Regeneration”. Dr. Nuria Montserrat  is also the coordinator of the Platform for Biobanks and Biomodels from the Institute of Health Carlos III (ISCIII PBB). Through its unique composition the ISCIII PBB is as an infrastructure able to perform, with a scientific, technological and regulatory perspective, a complete preclinical validation from the design to the product to its in vivo validation. To achieve this the IBEC has structured all the UNITS conforming the Platform in four different HUBS to ensure a transversal role throughout the entire R&D&I value chain including: 3D BIOMODELS (19 UNITS), BIOBANKS (57 BIOBANKS), 3D PRINTING (19 UNITS), ANIMAL MODELS (19 UNITS). The ISCIII PBB is the Spain National Node’s of the European biobank infrastructure (BBMRI-ERIC). The participation of the ISCIII PBB in REACT will guarantee the procurement of samples and associated data for the proper development of WP2.

The Technical University of Denmark, DTU coordinates the WP5 within REACT. Through the participation of Dr. Sine Reker, director of the laboratory “T cells and Cancer”. The T cells and Cancer is devoted to characterize T cell recognition in the context of diseases – as such we the group has contributed significantly to the development of multiplex strategies for T cell detection to comprehensively evaluate T cell reactivity in both cancer and autoimmune diseases.

Novel technologies developed in the group have changed the paradigm for T cell detection by introducing a molecular tagging system (DNA barcoding) – this allows simultaneous detection of >1,000 different antigen responding T cells.  The research team is currently using this technology to unravel the immune reactivity towards cancer associate neo- and shared epitopes, as well as understanding the influence of cancer therapy on the immune recognition. Throughout these studies, the research team has already been able to dissect the epitope specific recognition of clinical relevant T cells, and provide novel insight on how tumors can precisely be targeted through immunotherapy.

The team has also built novel technology platforms that allow in-depth understanding of T cell recognition from a structural perspective, which can be used to evaluate clinical efficacy and safety profiles of T cell receptors for clinical use.

Rigshospitalet leads WP4 and WP9 within REACT. Furthermore, Righospitalet also participates in WP2, WP6 and WP9. 

Dr. Sisse R. Ostrowski leads WP4 and participates in WP2. Importantly, the group of Dr. Sisse R. Ostrowski  is focused on translational research in precision medicine through biobanks and large-scale genetic-epidemiologic and biomarker studies. The group has a focus on the development of immunopprofiling as a diagnostic tool for tailored care in patients with (suspect) immune dysfunction or undergoing immunomodulating interventions, mapping iatrogenic- and host factors interacting with the immunophenotype.

In WP9 the group of Dr. Susanne Dam Poulsen from the Department of Infectious Disease of Rigshospitalet will test new prognostic biomarkers and potential treatments. Under the lead of Dr. Dam Poulsen biomarkers identified in WP4-8 will be integrated in algorithms to identify patients in need of a given treatment. Further work will involve preparing genetic and adaptive trial protocols that are conditionally pre-approved by ethics and regulatory authorities

Likewise, through the participation of Dr. Peter Garred, the scientific coordinator of Rigshospitalet and leader of the Laboratory of Medicine, REACT will count with expertise on understanding the structure and molecular genetics of the complement system in general and the lectin pathway in particular. This understanding will be fundamental for the proper development of WP5 and WP6. Importantely, during the COVID-19 pandemic,  Peter Garred Laboratory developed multiple serological and cell-based assays to investigate the humoral and cellular immune responses against SARS-CoV-2 and vaccine responses and expanded focus to B and T cell immunity. The research team is experienced in the expression and production of recombinant proteins as well as the production of monoclonal antibodies. Moreover, the aforementioned setup enables large-scale serological and cellular immune analyses on different platforms. 

Statens Serum Institut (Copenhagen, Denmark) is the coordinating country of REACT, and has two departments involved in the project.

On one hand, through the project coordinator (PC), Dr. Maria Vistrup-Parry, who integrates the Danish National Biobank, which stores more than 14 million biological samples and is thus one of the world’s largest biobanks. The Biobank is a unique resource nationally and internationally and of great use to research in disease pathogenesis, prevention and treatment. The Danish National Biobank strengthens Danish research infrastructure and thus the opportunities for Danish health research and international collaboration.

On the other hand, from SSI, there is the participation from the Department of Virus & Microbiological Special Diagnostics (VMS), which is the national central laboratory for human virology, including surveillance of viral infections, and research and development within the field. The department comprises the national WHO Centres on influenza, polio and measles/rubella. The department is also a member of the European Network for Imported Viral Diseases (ENIVD), thus participating in the European collaboration on surveillance of viral infections.

The participation of both departments is therefore crucial for the management of REACT, storing and sharing of samples, and the characterization and isolation of the circulating variants of SARS-CoV-2, influenza, and RSV.