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The proteolytic airway environment associated with pneumonia acts as a barrier for treatment with anti-infective antibodies.
Blin, Timothée; Parent, Christelle; Pichon, Gabrielle; Guillon, Antoine; Jouan, Youenn; Allouchi, Hassan; Aubrey, Nicolas; Boursin, Fanny; Domain, Roxane; Korkmaz, Baris; Sécher, Thomas; Heuzé-Vourc'h, Nathalie.
Afiliação
  • Blin T; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France; Tours University Hospital (CHRU), Department of Pulmonary Medicine, Cystic Fibrosis Resource Center, F-37032 Tours, France.
  • Parent C; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France.
  • Pichon G; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France.
  • Guillon A; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France; Tours University Hospital (CHRU), Critical Care Department, F-37032 Tours, France.
  • Jouan Y; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France; Tours University Hospital (CHRU), Cardiac Surgery Department, F-37032 Tours, France.
  • Allouchi H; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France; Tours University Hospital (CHRU), Pharmacy Department, F-37032 Tours, France.
  • Aubrey N; University of Tours, F-37032 Tours, France; UMR INRA ISP 1282, BioMap Team, F-37032 Tours, France.
  • Boursin F; University of Tours, F-37032 Tours, France; UMR INRA ISP 1282, BioMap Team, F-37032 Tours, France.
  • Domain R; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France.
  • Korkmaz B; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France.
  • Sécher T; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France.
  • Heuzé-Vourc'h N; INSERM, Respiratory Disease Research Centre, U1100, F-37032 Tours, France; University of Tours, F-37032 Tours, France. Electronic address: nathalie.heuze@med.univ-tours.fr.
Eur J Pharm Biopharm ; 195: 114163, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38086491
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia / COVID-19 Limite: Humans Idioma: En Revista: Eur J Pharm Biopharm Assunto da revista: FARMACIA / FARMACOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pneumonia / COVID-19 Limite: Humans Idioma: En Revista: Eur J Pharm Biopharm Assunto da revista: FARMACIA / FARMACOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França