Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection

  • 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.

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Author:Sandro HalweORCiD, Alexandra KupkeORCiD, Kanika VanshyllaORCiD, Falk LibertaORCiDGND, Henning GrüllORCiDGND, Matthias ZehnerORCiDGND, Cornelius RohdeORCiD, Verena KrählingORCiDGND, Michelle Gellhorn SerraORCiD, Christoph KreerORCiDGND, Michael KlüverORCiD, Lucie SauerheringORCiDGND, Jörg SchmidtORCiD, Zheng Cai, Fei Han, David Young, Guangwei Yang, Marek WideraORCiDGND, Manuel KochORCiD, Anke WernerORCiD, Lennart Kämper, Nico Becker, Michael S. Marlow, Markus Eickmann, Sandra CiesekORCiDGND, Felix Schiele, Florian Klein, Stephan BeckerORCiDGND
Parent Title (English):Viruses
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/07/29
Date of first Publication:2021/07/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/07/04
Tag:SARS-CoV-2; animal experiments; intranasal administration; mice; monoclonal antibody; neutralizing antibody; topical administration; transduction; virus
Issue:8, art. 1498
Article Number:1498
Page Number:21
First Page:1
Last Page:21
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0