2. Academic Validation
  3. Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

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

  • Viruses. 2021 Jul 29;13(8):1498. doi: 10.3390/v13081498.
Sandro Halwe 1 2,  Alexandra Kupke 1 2,  Kanika Vanshylla 3,  Falk Liberta 4,  Henning Gruell 3,  Matthias Zehner 3,  Cornelius Rohde 1 2,  Verena Krähling 1 2,  Michelle Gellhorn Serra 1 2,  Christoph Kreer 3,  Michael Klüver 1 2,  Lucie Sauerhering 1 2,  Jörg Schmidt 1 2,  Zheng Cai 5,  Fei Han 5,  David Young 5,  Guangwei Yang 5,  Marek Widera 6,  Manuel Koch 7 8,  Anke Werner 1,  Lennart Kämper 1,  Nico Becker 1,  Michael S Marlow 5,  Markus Eickmann 1,  Sandra Ciesek 6 9 10,  Felix Schiele 4,  Florian Klein 3 7 11,  Stephan Becker 1 2
Affiliations

Affiliations

  • 1 Institute of Virology, Philipps University Marburg, Hans-Meerwein-Straße 2, 35043 Marburg, Germany.
  • 2 German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, 35043 Marburg, Germany.
  • 3 Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • 4 Biotherapeutics Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
  • 5 Biotherapeutics Molecule Discovery, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
  • 6 Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60596 Frankfurt am Main, Germany.
  • 7 Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
  • 8 Institute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, University of Cologne, 50931 Cologne, Germany.
  • 9 German Center for Infection Research (DZIF), Partner Site Frankfurt am Main, 60596 Frankfurt am Main, Germany.
  • 10 Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine and Pharmacology, 60596 Frankfurt am Main, Germany.
  • 11 German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, Germany.
PMID: 34452363 DOI: 10.3390/v13081498
Abstract

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.

Keywords

SARS-CoV-2; animal experiments; intranasal administration; mice; monoclonal antibody; neutralizing antibody; topical administration; transduction; virus.

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