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

Autor: Beukenhorst AL; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. anna.beukenhorst@leydenlabs.com.; Leyden Laboratories BV, Leiden, The Netherlands. anna.beukenhorst@leydenlabs.com.; Centre for Epidemiology, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. anna.beukenhorst@leydenlabs.com., Frallicciardi J; Leyden Laboratories BV, Leiden, The Netherlands., Rice KL; Leyden Laboratories BV, Leiden, The Netherlands., Koldijk MH; Leyden Laboratories BV, Leiden, The Netherlands., Moreira de Mello JC; Leyden Laboratories BV, Leiden, The Netherlands., Klap JM; Leyden Laboratories BV, Leiden, The Netherlands., Hadjichrysanthou C; Department of Mathematics, University of Sussex, Brighton, UK., Koch CM; Leyden Laboratories BV, Leiden, The Netherlands., da Costa KAS; Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and University of Greenwich, Chatham, UK., Temperton N; Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and University of Greenwich, Chatham, UK., de Jong BA; Leyden Laboratories BV, Leiden, The Netherlands., Vietsch H; Leyden Laboratories BV, Leiden, The Netherlands., Ziere B; Leyden Laboratories BV, Leiden, The Netherlands., Julg B; Leyden Laboratories BV, Leiden, The Netherlands., Koudstaal W; Leyden Laboratories BV, Leiden, The Netherlands., Goudsmit J; Leyden Laboratories BV, Leiden, The Netherlands.; Departments of Epidemiology, Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Feb 15; Vol. 14 (1), pp. 3818. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1038/s41598-024-53049-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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