Universität zu Köln

Halwe, Sandro ORCID: 0000-0002-4021-7728, Kupke, Alexandra ORCID: 0000-0001-8517-4779, Vanshylla, Kanika ORCID: 0000-0003-4552-9170, Liberta, Falk, Gruell, Henning, Zehner, Matthias, Rohde, Cornelius ORCID: 0000-0002-4752-8326, Kraehling, Verena, Gellhorn Serra, Michelle ORCID: 0000-0002-0322-3555, Kreer, Christoph ORCID: 0000-0002-9140-9850, Kluever, Michael, Sauerhering, Lucie, Schmidt, Jorg, Cai, Zheng, Han, Fei, Young, David, Yang, Guangwei, Widera, Marek ORCID: 0000-0001-5417-9307, Koch, Manuel ORCID: 0000-0002-2962-7814, Werner, Anke, Kaemper, Lennart, Becker, Nico, Marlow, Michael S., Eickmann, Markus, Ciesek, Sandra ORCID: 0000-0002-1802-7565, Schiele, Felix, Klein, Florian and Becker, Stephan (2021). Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. Viruses-Basel, 13 (8). BASEL: MDPI. ISSN 1999-4915

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Halwe, Sandro UNSPECIFIED orcid.org/0000-0002-4021-7728 UNSPECIFIED Kupke, Alexandra UNSPECIFIED orcid.org/0000-0001-8517-4779 UNSPECIFIED Vanshylla, Kanika UNSPECIFIED orcid.org/0000-0003-4552-9170 UNSPECIFIED Liberta, Falk UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Zehner, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Rohde, Cornelius UNSPECIFIED orcid.org/0000-0002-4752-8326 UNSPECIFIED Kraehling, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Gellhorn Serra, Michelle UNSPECIFIED orcid.org/0000-0002-0322-3555 UNSPECIFIED Kreer, Christoph UNSPECIFIED orcid.org/0000-0002-9140-9850 UNSPECIFIED Kluever, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Sauerhering, Lucie UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Jorg UNSPECIFIED UNSPECIFIED UNSPECIFIED Cai, Zheng UNSPECIFIED UNSPECIFIED UNSPECIFIED Han, Fei UNSPECIFIED UNSPECIFIED UNSPECIFIED Young, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Guangwei UNSPECIFIED UNSPECIFIED UNSPECIFIED Widera, Marek UNSPECIFIED orcid.org/0000-0001-5417-9307 UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Werner, Anke UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaemper, Lennart UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Nico UNSPECIFIED UNSPECIFIED UNSPECIFIED Marlow, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eickmann, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Ciesek, Sandra UNSPECIFIED orcid.org/0000-0002-1802-7565 UNSPECIFIED Schiele, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596078
DOI:	10.3390/v13081498
Journal or Publication Title:	Viruses-Basel
Volume:	13
Number:	8
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1999-4915
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RESPIRATORY SYNDROME CORONAVIRUS; MOUSE MODELS; PHARMACOKINETICS; EFFICACY; DELIVERY; DISEASE; VIREMIA; HUMANS; IGG Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59607