Virtual MACS® COVID-19 Day

To give you an insight into the latest discoveries on SARS-CoV-2 and promote scientific networking, we hosted a virtual event full of interesting talks and round table discussions with several experts who will shared their latest findings in COVID-19 research. 

Thank you to those of you who attended the event, if you missed it or wish to listen again, we will have a selection of talks and roundtable discussions available for you to listen to within the next couple of weeks.

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Cytokine Capture System for SARS-CoV-2 specific T cells 

Professor Leung Wing Hang 
KK Women’s and Children’s Hospital, Singapore.

SARS-CoV-2-specific T cells are crucial for virus control in COVID-19. A central hypothesis is that SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be manufactured expeditiously and are safe and effective for the treatment of severe SARS-CoV-2 infections in recipients. In this talk, Prof Leung will discuss rapid manufacturing of clinical-grade SARS-CoV-2-specific T cells for adoptive cell therapy. High frequencies of peptide-reactive T cells were found in convalescent donors, regardless of severity of COVID-19.

The role of C5a-C5aR1 in COVID-19

Professor Eric Vivier 
Chief Scientific Officer, Innate Pharma. Professor of Immunology, Aix Marseille Université, France.

COVID-19 is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2.

The C5a anaphylatoxin and its receptor C5aR1 (CD88) play a key role in the initiation and maintenance of several inflammatory responses, by recruiting and activating neutrophils and monocytes in the lungs1. We provide a longitudinal analysis of immune responses, including immune cell phenotyping and assessments of the soluble factors present in the blood and broncho-alveolar lavage fluid (BALF) of patients at various stages of COVID-19 severity: paucisymptomatic, pneumonia and acute respiratory distress syndrome (ARDS). We report an increase in soluble C5a levels proportional to COVID-19 severity and high levels of C5aR1 expression in blood and pulmonary myeloid cells, supporting a role for the C5a-C5aR1 axis in the pathophysiology of ARDS. Anti-C5aR1 therapeutic monoclonal antibodies (mAbs) prevented C5a-mediated human myeloid cell recruitment and activation and inhibited acute lung injury (ALI) in human C5aR1 knockin mice.

These results suggest that C5a-C5aR1 axis blockade might be used as a means of limiting myeloid cell infiltration in damaged organs and preventing the excessive lung inflammation and endothelialitis associated with ARDS in COVID-19 patients.

Deep profiling of SARS-CoV-2-specific T cells from healthy donors and COVID-19 patients using ARTE

Professor Alexander Scheffold
Institute of Immunology, Christian-Albrechts-Universität zu Kiel, Germany.

 

SARS-CoV-2 proteins and analysis of humoral immunity in COVID-19 patients

Dr. Susanne Bethke
Global Product Manager, Miltenyi Biotec

Cellular and humoral immunity are important immune responses against SARS-CoV-2.Virus clearance and inflammation are mainly mediated by CD8+ T cells directed against the SARS-CoV-2 spike protein. However, the total lymphocyte population, as well as CD4+ T cells, B cells, and natural killer have shown to play a significant role in COVID-19 inflammatory status.Currently it is unknown which responses confer protection against COVID-19.

The dynamics of antibody response against SARS-CoV-2 are under investigation and detection of SARS-CoV-2-specific antibodies are no direct indication forprotective immunity. Nevertheless, most of infected patients show an antibody response between day 7 and 21 after infection. Notably, the longevity of the antibody responseis considered to be correlated with protective immunity against reinfections, which is important information when considering the formulation of vaccines.

There are still many studies required to fully understand the role of the humoral immune response against SARS-CoV-2. Although serum antibodies are thought to decrease over time, mucosal antibodies, such as IgA, are thought to persist, as demonstrated for seasonal coronavirus 229E. A lot of questions remain unanswered. What level and which type of antibodyis needed for protection? Which target antigenis most protective? What are important antibody dynamics? Which B cells produce these kinds of antibodies? And, might some antibodies enhance the disease? Prolonged studies and more research are therefore required in order to clarify these and many other open questions. To undertake such research, it is vital to have high quality SARS-CoV-2 proteins. We’ll present here the work that has been carried out at Miltenyi Biotec to produce and test full length SARS-CoV-2 proteins and the humoral responses of patients against them. 

 

Innate immunity against SARS-CoV-2 

Professor Andrea Cossarizza 
Department of Medical and Surgical Sciences for Children and Adults, 
University of Modena and Reggio Emilia School of Medicine, Italy.

The infection SARS-CoV-2 is able to alter several functions of different immune cells. We have first described what happens in the T and in the B cell compartments, where a relevant functional exhaustion exists in patients with COVID-19 pneumonia. We have then explored alterations present among cells belonging to the innate immunity branch. Monocytes are heavily impaired as well, and indeed they show signs of altered bioenergetics and mitochondrial dysfunction. We also identified a consistent redistribution of monocyte subsets in the blood, with a significant expansion of intermediate/pro-inflammatory cells, a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints, including PD-1/PD-L1.

 

Treg cell therapy as a new approach to prevent the immune hyperactivation responsible for the clinical worsening of COVID-19

Professor Rafael Correa Rocha 
Head of Laboratory, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Spain.

The clinical worsening in COVID-19 patients is a consequence of the immunopathology induced by a cytokine release syndrome, associated with the immune response against the virus, which in the most severe cases can trigger multi-organ failure and death of the patient.

Cell therapy with Treg cells can potentially be a successful approach to treat or prevent the immune hyperactivation, and their suppressive capacity can be the best option for the control of the hyperinflammatory phase. Our group has experience in the clinical employment of Treg cell therapy for the control of immune related diseases, employing pioneering approaches that will allow scaling and therapeutic use in large patient groups.

The signature of anti-viral T cell immunity in COVID-19 patients and healthy controls: Analysis of frequency, specificity, functionality and phenotype in the course of disease and recovery 

Professor Britta Eiz-Vesper 
Institute for Transfusion Medicine and Transplant Engineering, alloCELL Labor and T cell donation register, Medical School Hanover, Germany.

 

Managing cell sorting of biohazardous samples during the COVID-19 pandemic

David Leclerc 
CYM(ASCP) Technical Director, Cytometry Antibody Technologies Facility, The University of Chicago, USA.

The Cytometry and Antibody Technology Facility (CAT) at the University of Chicago received a new MACSQuant Tyto cell sorter in March of 2020, just as the activities in the laboratory were being drastically reduced due to the COVID-19 crisis. Yet, the Tyto became a critical component of the research projects of groups working on that virus. This discussion will provide an overview of the CAT Facility, the circumstances by which the Tyto was acquired, how it became a major part of the way we handle biohazardous material in our research environment, and how we plan to position the Tyto going forward.

Highlights

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