The proteolytic airway environment associated with pneumonia acts as a barrier for treatment with anti-infective antibodies
2024
Blin, Timothée | Parent, Christelle | Pichon, Gabrielle | Guillon, Antoine | Jouan, Youenn | Allouchi, Hassan | Aubrey, Nicolas | Boursin, Fanny | Domain, Roxane | Korkmaz, Baris | Secher, Thomas | Heuzé-Vourc’h, Nathalie | Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR) ; Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) | Département de Pharmacologie [CHRU Tours] ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) | Infectiologie et Santé Publique (ISP) ; Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. Like pneumonia, coronavirus disease 2019 (COVID-19) is characterized by a massive infiltration of innate immune cells (such as polymorphonuclear leukocytes) into the airways and alveolar spaces. These cells release proteases that may degrade therapeutic antibodies and thus limit their effectiveness. Here, we investigated the in vitro and ex vivo impact on anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) IgG1s and other IgG subclasses (IgG2 and IgG4) of the neutrophil elastase, proteinase 3 and cathepsin G (the three main neutrophil serine proteases) found in endotracheal aspirates from patients with severe COVID-19. Although the IgGs were sensitive to neutrophil serine proteases, IgG2 was most resistant to proteolytic degradation. The two anti-SARS CoV2 antibodies (casirivimab and imdevimab) were sensitive to the lung's proteolytic environment, although neutrophil serine protease inhibitors only partly limited the degradation. Overall, our results show that the pneumonia-associated imbalance between proteases and their inhibitors in the airways contributes to degradation of antiviral antibodies.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique