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A pan-influenza monoclonal antibody neutralizes H5 strains and prophylactically protects through intranasal administration

Beukenhorst, Anna L., Frallicciardi, Jacopo, Rice, Keira L., Koldijk, Martin H., Moreira de Mello, Joana C., Klap, Jaco M., Hadjichrysanthou, Christoforos, Koch, Clarissa M., da Costa, Kelly A. S., Temperton, Nigel, and others. (2024) A pan-influenza monoclonal antibody neutralizes H5 strains and prophylactically protects through intranasal administration. Scientific Reports, 14 (1). Article Number 3818. ISSN 2045-2322. (doi:10.1038/s41598-024-53049-5) (KAR id:105021)

Abstract

Avian A(H5N1) influenza virus poses an elevated zoonotic threat to humans, and no pharmacological products are currently registered for fast-acting pre-exposure protection in case of spillover leading to a pandemic. Here, we show that an epitope on the stem domain of H5 hemagglutinin is highly conserved and that the human monoclonal antibody CR9114, targeting that epitope, potently neutralizes all pseudotyped H5 viruses tested, even in the rare case of substitutions in its epitope. Further, intranasal administration of CR9114 fully protects mice against A(H5N1) infection at low dosages, irrespective of pre-existing immunity conferred by the quadrivalent seasonal influenza vaccine. These data provide a proof-of-concept for broad, pre-exposure protection against a potential future pandemic using the intranasal administration route. Studies in humans should assess if autonomous administration of a broadly-neutralizing monoclonal antibody is safe and effective and can thus contribute to pandemic preparedness.

Item Type: Article
DOI/Identification number: 10.1038/s41598-024-53049-5
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 16 Feb 2024 17:02 UTC
Last Modified: 19 Feb 2024 13:04 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/105021 (The current URI for this page, for reference purposes)

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