TY - JOUR A1 - Halwe, Sandro A1 - Kupke, Alexandra A1 - Vanshylla, Kanika A1 - Liberta, Falk A1 - Grüll, Henning A1 - Zehner, Matthias A1 - Rohde, Cornelius A1 - Krähling, Verena A1 - Gellhorn Serra, Michelle A1 - Kreer, Christoph A1 - Klüver, Michael A1 - Sauerhering, Lucie A1 - Schmidt, Jörg A1 - Cai, Zheng A1 - Han, Fei A1 - Young, David A1 - Yang, Guangwei A1 - Widera, Marek A1 - Koch, Manuel A1 - Werner, Anke A1 - Kämper, Lennart A1 - Becker, Nico A1 - Marlow, Michael S. A1 - Eickmann, Markus A1 - Ciesek, Sandra A1 - Schiele, Felix A1 - Klein, Florian A1 - Becker, Stephan T1 - Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection T2 - Viruses N2 - 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. KW - SARS-CoV-2 KW - monoclonal antibody KW - neutralizing antibody KW - virus KW - animal experiments KW - mice KW - transduction KW - intranasal administration KW - topical administration Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62189 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621896 SN - 1999-4915 VL - 13.2021 IS - 8, art. 1498 SP - 1 EP - 21 PB - MDPI CY - Basel ER -