The proteolytic airway environment associated with pneumonia acts as a barrier for treatment with anti-infective antibodies

Eur J Pharm Biopharm. 2023 Dec 10:S0939-6411(23)00327-2. doi: 10.1016/j.ejpb.2023.12.003. Online ahead of print.ABSTRACTLike 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.PMID:38086491 | DOI:10.1016/j.ejpb.2023.12.003

Source: European Journal of Pharmaceutics and Biopharmaceutics - December 12, 2023 Category: Drugs & Pharmacology Authors: Timoth ée Blin Christelle Parent Gabrielle Pichon Antoine Guillon Youenn Jouan Hassan Allouchi Nicolas Aubrey Fanny Boursin Roxane Domain Baris Korkmaz Thomas S écher Nathalie Heuz é-Vourc'h Source Type: research