Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination

In 2024, a clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) emerged in dairy cattle in the United States and spread rapidly to over 1,000 herds across multiple states. At least 41 human infections have occurred through contact with infected cattle, though no fatalities have been r...

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Main Authors: Lu Zhang, Georg M. N. Behrens, Amy Kempf, Inga Nehlmeier, Sabine Gärtner, Anna-Sophie Moldenhauer, Luise Graichen, Christine Happle, Michael Winkler, Alexandra Dopfer-Jablonka, Stefan Pöhlmann, Markus Hoffmann
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Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2528539
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author Lu Zhang
Georg M. N. Behrens
Amy Kempf
Inga Nehlmeier
Sabine Gärtner
Anna-Sophie Moldenhauer
Luise Graichen
Christine Happle
Michael Winkler
Alexandra Dopfer-Jablonka
Stefan Pöhlmann
Markus Hoffmann
author_facet Lu Zhang
Georg M. N. Behrens
Amy Kempf
Inga Nehlmeier
Sabine Gärtner
Anna-Sophie Moldenhauer
Luise Graichen
Christine Happle
Michael Winkler
Alexandra Dopfer-Jablonka
Stefan Pöhlmann
Markus Hoffmann
author_sort Lu Zhang
collection DOAJ
description In 2024, a clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) emerged in dairy cattle in the United States and spread rapidly to over 1,000 herds across multiple states. At least 41 human infections have occurred through contact with infected cattle, though no fatalities have been reported so far. This raises questions about whether the human innate immune system provides a barrier to bovine H5N1 HPAIV and whether seasonal influenza vaccines offer cross-protection. To address these questions, we used pseudoviruses bearing hemagglutinin (HA) and neuraminidase (NA) from seasonal influenza A or various H5Ny HPAIV strains (from cattle, duck, and seal). Pseudoviruses bearing H5N1 HPAIV HA and NA entered a wide range of mammalian and avian cell lines, including multiple cell lines from the human respiratory tract, while entry into A549 human lung cells was reduced when IFITM proteins were expressed. Additionally, preincubation of pseudovirus particles bearing H5N1 HPAIV HA and NA with plasma from individuals vaccinated with seasonal influenza vaccines inhibited viral entry. Collectively, these results suggest that the human innate immune system imposes a barrier against bovine H5N1 HPAIV infection and that seasonal influenza vaccines can induce cross-neutralizing activity against bovine H5N1 HPAIV.
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spelling doaj-art-0b5e0472cf7f41f28d0a97642df2673e2025-08-20T02:47:13ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2528539Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccinationLu Zhang0Georg M. N. Behrens1Amy Kempf2Inga Nehlmeier3Sabine Gärtner4Anna-Sophie Moldenhauer5Luise Graichen6Christine Happle7Michael Winkler8Alexandra Dopfer-Jablonka9Stefan Pöhlmann10Markus Hoffmann11Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyInfection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, GermanyIn 2024, a clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) emerged in dairy cattle in the United States and spread rapidly to over 1,000 herds across multiple states. At least 41 human infections have occurred through contact with infected cattle, though no fatalities have been reported so far. This raises questions about whether the human innate immune system provides a barrier to bovine H5N1 HPAIV and whether seasonal influenza vaccines offer cross-protection. To address these questions, we used pseudoviruses bearing hemagglutinin (HA) and neuraminidase (NA) from seasonal influenza A or various H5Ny HPAIV strains (from cattle, duck, and seal). Pseudoviruses bearing H5N1 HPAIV HA and NA entered a wide range of mammalian and avian cell lines, including multiple cell lines from the human respiratory tract, while entry into A549 human lung cells was reduced when IFITM proteins were expressed. Additionally, preincubation of pseudovirus particles bearing H5N1 HPAIV HA and NA with plasma from individuals vaccinated with seasonal influenza vaccines inhibited viral entry. Collectively, these results suggest that the human innate immune system imposes a barrier against bovine H5N1 HPAIV infection and that seasonal influenza vaccines can induce cross-neutralizing activity against bovine H5N1 HPAIV.https://www.tandfonline.com/doi/10.1080/22221751.2025.2528539H5N1clade 2.3.4.4bbovineneutralizationseasonal influenza vaccination
spellingShingle Lu Zhang
Georg M. N. Behrens
Amy Kempf
Inga Nehlmeier
Sabine Gärtner
Anna-Sophie Moldenhauer
Luise Graichen
Christine Happle
Michael Winkler
Alexandra Dopfer-Jablonka
Stefan Pöhlmann
Markus Hoffmann
Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination
Emerging Microbes and Infections
H5N1
clade 2.3.4.4b
bovine
neutralization
seasonal influenza vaccination
title Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination
title_full Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination
title_fullStr Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination
title_full_unstemmed Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination
title_short Neutralizing activity against bovine H5N1 HPAIV (clade 2.3.4.4b) in human plasma after seasonal influenza vaccination
title_sort neutralizing activity against bovine h5n1 hpaiv clade 2 3 4 4b in human plasma after seasonal influenza vaccination
topic H5N1
clade 2.3.4.4b
bovine
neutralization
seasonal influenza vaccination
url https://www.tandfonline.com/doi/10.1080/22221751.2025.2528539
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