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

by Rice, Keira L. , Klap, Jaco M. , Frallicciardi, Jacopo , de Jong, Babette A. , Beukenhorst, Anna L. , Ziere, Bertjan , da Costa, Kelly A. S. , Vietsch, Helene , Julg, Boris , Goudsmit, Jaap , Temperton, Nigel , Koudstaal, Wouter , Koldijk, Martin H. , Koch, Clarissa M. , Moreira de Mello, Joana C. , Hadjichrysanthou, Christoforos

in 631/61/51/1568 / 692/308/153 / 692/308/575 / 692/699/255/1578 / 692/699/255/2514 / 692/700/478 / Administration, Intranasal / Animals / Antibodies, Monoclonal / Antibodies, Neutralizing / Antibodies, Viral / Avian flu / Epidemics / Epidemiology / Epitopes / Hemagglutinin Glycoproteins, Influenza Virus / Hemagglutinins / Humanities and Social Sciences / Humans / Infections / Influenza / Influenza A Virus, H5N1 Subtype / Influenza Vaccines / Influenza, Human / Intranasal administration / Mice / Mice, Inbred BALB C / Monoclonal antibodies / multidisciplinary / Mutation / Pandemics / Phylogenetics / Poultry / Public health / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Vaccines / Viruses / Zoonoses

2024

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2024

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2024

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Journal Article

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

Rice, Keira L.,

Klap, Jaco M.,

Frallicciardi, Jacopo,

de Jong, Babette A.,

Beukenhorst, Anna L.,

Ziere, Bertjan,

da Costa, Kelly A. S.,

Vietsch, Helene,

Julg, Boris,

Goudsmit, Jaap,

Temperton, Nigel,

Koudstaal, Wouter,

Koldijk, Martin H.,

Koch, Clarissa M.,

Moreira de Mello, Joana C.,

Hadjichrysanthou, Christoforos

2024

Overview

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.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ Administration, Intranasal