Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

Viruses

Falk Liberta¹  Felix Schiele¹  Michael S. Marlow²  Guangwei Yang²  David Young²  Zheng Cai²  Fei Han²  Manuel Koch³  Marek Widera⁴  Sandra Ciesek⁴  Kanika Vanshylla⁵  Matthias Zehner⁵  Henning Gruell⁵  Florian Klein⁵  Christoph Kreer⁵  Sandro Halwe⁶  Jörg Schmidt⁶  Michael Klüver⁶  Markus Eickmann⁶  Cornelius Rohde⁶  Nico Becker⁶  Anke Werner⁶  Alexandra Kupke⁶  Lennart Kämper⁶  Michelle Gellhorn Serra⁶  Verena Krähling⁶  Stephan Becker⁶  Lucie Sauerhering⁶ 

[1] Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany;Biotherapeutics Molecule Discovery, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA;Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany;Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60596 Frankfurt am Main, Germany;Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany;Institute of Virology, Philipps University Marburg, Hans-Meerwein-Straße 2, 35043 Marburg, Germany;

关键词: SARS-CoV-2;    monoclonal antibody;    neutralizing antibody;    virus;    animal experiments;    mice;   

DOI  :  10.3390/v13081498

来源: DOAJ

【 摘 要 】

Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of the SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2, retains full activity against the variant of concern (VOC) B.1.1.7 and still neutralizes the VOC B.1.351, although with reduced potency. Importantly, not only systemic but also intranasal application of DZIF-10c abolished the presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology when administered prophylactically. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.

【 授权许可】

Unknown