SARS-CoV-2 neutralization and protection of hamsters via nasal administration of a humanized neutralizing antibody
Lebedin M. Petrovsky N. Tabynov K. Tabynov K. Lebedin Y.
September 2025Elsevier B.V.
Antiviral Research
2025#241
Monoclonal antibodies are widely used for the treatment of infectious human diseases, including COVID-19. Since the start of the pandemic, eight monoclonal antibodies against SARS-CoV-2 were granted emergency use authorization. The high mutation rate of the SARS-CoV-2 virus has led to the emergence of highly transmissible variants that can evade vaccine-induced immunity. In this study, we generated a panel of murine monoclonal antibodies (mAb) to identify a subset that broadly neutralized SARS-CoV-2 variants and explored whether mucosal administration of such antibodies could protect against infection. Intranasal delivery of XR10, the most promising murine mAb, protected hamsters against infection by Delta variant. We next humanized XR10 mAb using a combination of CDR-grafting and Vernier zones preservation approaches (CRVZ) to create a panel of humanized XR10 variants. We ranked the variants based on their spike binding ability and virus neutralization. Of these, XR10v48 demonstrated the best ability to neutralize SARS-CoV-2 variants and was protective in hamsters when given as a single 50 μg/kg intranasal dose at the time of viral challenge. XR10v48 featured 34 key amino acid residues retained from the murine progenitor. With SARS-CoV-2 escape mutants continuing to emerge this work highlights a potential workflow to generate humanized broadly cross-neutralizing mAb for potential use as a nasal spray for SARS-CoV-2 prophylaxis.
Antibody humanization , COVID-19 , Intranasal administration , Prophylactic protective antibody , SARS-CoV-2 antibodies
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Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, 13125, Germany
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, Berlin, 10117, Germany
Vaxine Pty Ltd, 11 Walkley Avenue, Warradale, 5046, Australia
International Center for Vaccinology, Kazakh National Agrarian Research University, 8 Abay Avenue, Almaty, 050010, Kazakhstan
Preclinical Research Laboratory with Vivarium, M. Aikimbayev National Research Center for Especially Dangerous Infections, 14 Zhakhanger str., Almaty, 050054, Kazakhstan
Republican Allergy Center, Research Institute of Cardiology and Internal Medicine, 120 Aiteke bi str., Almaty, 050000, Kazakhstan
Xema Oy, Myllymäenkatu 21, Lappeenranta, 53550, Finland
Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Charité – Universitätsmedizin Berlin
Vaxine Pty Ltd
International Center for Vaccinology
Preclinical Research Laboratory with Vivarium
Republican Allergy Center
Xema Oy
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