FIRST PATIENT DOSED IN AVDORALIMAB PHASE II CLINICAL TRIAL IN COVID-19 PATIENTS WITH SEVERE PNEUMONIA

Initial translational analysis, EXPLORE, showed overexpression of C5a/C5aR pathway in patients with severe COVID-19
The primary objective of this investigator-sponsored trial, named FORCE, is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).

“Through the translational data analysis in COVID-19 patients, we observed high levels of circulating C5a and over-activation of the C5a-dependent myeloid cell pathway, which is believed to contribute to inflammation in the lungs. Avdoralimab is a monoclonal antibody that blocks C5aR and has the potential to reduce the inflammatory response in the lungs,” said Pr. Eric Vivier, PhD, Chief Scientific Officer at Innate Pharma and Professor at AP-HM (Marseille Public University Hospitals), Aix-Marseille University and Centre d’Immunologie de Marseille-Luminy, CNRS, Inserm and AMU.
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A newly discovered memory in our bones: blood stem cells boost immunity by keeping a record of previous infections

A Franco-German research team led by Prof. Michael Sieweke, from the Center for Regenerative Therapies TU Dresden (CRTD) and the Center of  Immunology of Marseille Luminy (CNRS, INSERM, Aix-Marseille University), today uncovered a surprising property of blood stem cells: not only do they ensure the continuous renewal of blood cells and contribute to the immune response triggered by an infection, but they can also remember previous infectious encounters to drive a more rapid and more efficient immune response in the future. These findings should have a significant impact on future vaccination strategies and pave the way for new treatments of an underperforming or over-reacting immune system. The results of this research are published in Cell Stem Cell on March 12, 2020. More information

C/EBPβ-Dependent Epigenetic Memory Induces Trained Immunity in Hematopoietic Stem Cells
de Laval B., Maurizio J., Kandalla P K., Brisou G., Simonnet L., Huber C., Gimenez G., Matcovitch-Natan O., Reinhardt S., David E., Mildner A., Leutz A., Nadel B., Bordi C., Amit I., Sarrazin S.*,†., Sieweke M H.*,†. Cell Stem Cell, 2020 , pii: S1934-5909(20)30017-5, PMID: 32169166

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When Stress Weakens the Immune Defenses

In previous years, various studies have established a link between psychological stress and reduced immune defenses, but the mechanisms involved remained poorly elucidated. Sophie Ugolini, Inserm Research Director at the Center of Immunology Marseille-Luminy, and her colleagues at CNRS and Aix-Marseille Université have recently shown that such a link is to a large extent mediated by a type of receptor that binds to stress hormones: the β2-adrenergic receptor. Their findings have been published in Journal of Experimental Medicine. More information

β2-adrenergic signals downregulate the innate immune response and reduce host resistance to viral infection Wieduwild E, Girard-Madoux MJ, Quatrini L, Laprie C, Chasson L, Rossignol R, Bernat C, Guia S, Ugolini S. J Exp Med., 2020 , 217(4), PMID: 32045472