IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58504-z.html
   My bibliography  Save this article

Intranasal influenza virus-vectored vaccine offers protection against clade 2.3.4.4b H5N1 infection in small animal models

Author

Listed:
  • Ying Liu

    (The University of Hong Kong
    The University of Hong Kong)

  • Shaofeng Deng

    (The University of Hong Kong
    The University of Hong Kong)

  • Shuang Ren

    (The University of Hong Kong
    The University of Hong Kong)

  • Rachel Chun-Yee Tam

    (The University of Hong Kong
    The University of Hong Kong)

  • Siwen Liu

    (The University of Hong Kong
    The University of Hong Kong)

  • Anna Jinxia Zhang

    (The University of Hong Kong
    The University of Hong Kong)

  • Kelvin Kai-Wang To

    (The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong)

  • Kwok-Yung Yuen

    (The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong)

  • Honglin Chen

    (The University of Hong Kong
    The University of Hong Kong)

  • Pui Wang

    (The University of Hong Kong
    The University of Hong Kong)

Abstract

The highly pathogenic avian influenza (HPAI) H5N1 virus has been endemic in aquatic birds since 1997, causing outbreaks in domestic poultry and occasional human infections worldwide. Recently, the cross-species transmission of a new reassortant variant from clade 2.3.4.4b of H5N1 to cattle in the US has heightened concerns regarding the expansion of host range and potential human infection. As eradicating the H5N1 virus from its reservoir is impossible, it is essential to prepare for a potential pandemic caused by an H5N1 derivative. Utilizing a deleted-NS1 live attenuated influenza viral vector vaccine system (DelNS1 LAIV), a system we have previously used in the development of a COVID-19 vaccine, we have rapidly developed an intranasal vaccine for cattle H5N1 and related clade 2.3.4.4b strains, based on publicly available sequences. Our research demonstrates that a single intranasal immunization can provide effective protection against lethal challenges from HPAI cattle or mink H5N1 variants, offering strong, sustained immunity after two months in female mouse and male hamster models. Immunogenicity analysis reveals that intranasal vaccination with DelNS1 LAIV induces robust neutralizing antibody, mucosal IgA and T cell responses in mice. It is crucial to further evaluate the DelNS1-H5N1 LAIV system to prepare for potential future H5N1 outbreaks in humans.

Suggested Citation

  • Ying Liu & Shaofeng Deng & Shuang Ren & Rachel Chun-Yee Tam & Siwen Liu & Anna Jinxia Zhang & Kelvin Kai-Wang To & Kwok-Yung Yuen & Honglin Chen & Pui Wang, 2025. "Intranasal influenza virus-vectored vaccine offers protection against clade 2.3.4.4b H5N1 infection in small animal models," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58504-z
    DOI: 10.1038/s41467-025-58504-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58504-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58504-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Wenjun Song & Pui Wang & Bobo Wing-Yee Mok & Siu-Ying Lau & Xiaofeng Huang & Wai-Lan Wu & Min Zheng & Xi Wen & Shigui Yang & Yu Chen & Lanjuan Li & Kwok-Yung Yuen & Honglin Chen, 2014. "The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    2. Amie J. Eisfeld & Asim Biswas & Lizheng Guan & Chunyang Gu & Tadashi Maemura & Sanja Trifkovic & Tong Wang & Lavanya Babujee & Randall Dahn & Peter J. Halfmann & Tera Barnhardt & Gabriele Neumann & Ya, 2024. "Pathogenicity and transmissibility of bovine H5N1 influenza virus," Nature, Nature, vol. 633(8029), pages 426-432, September.
    3. Leonardo C. Caserta & Elisha A. Frye & Salman L. Butt & Melissa Laverack & Mohammed Nooruzzaman & Lina M. Covaleda & Alexis C. Thompson & Melanie Prarat Koscielny & Brittany Cronk & Ashley Johnson & K, 2024. "Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle," Nature, Nature, vol. 634(8034), pages 669-676, October.
    4. Marina R. Good & Monica L. Fernández-Quintero & Wei Ji & Alesandra J. Rodriguez & Julianna Han & Andrew B. Ward & Jenna J. Guthmiller, 2024. "A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. K. S. Li & Y. Guan & J. Wang & G. J. D. Smith & K. M. Xu & L. Duan & A. P. Rahardjo & P. Puthavathana & C. Buranathai & T. D. Nguyen & A. T. S. Estoepangestie & A. Chaisingh & P. Auewarakul & H. T. Lo, 2004. "Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia," Nature, Nature, vol. 430(6996), pages 209-213, July.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Marcela M. Uhart & Ralph E. T. Vanstreels & Martha I. Nelson & Valeria Olivera & Julieta Campagna & Victoria Zavattieri & Philippe Lemey & Claudio Campagna & Valeria Falabella & Agustina Rimondi, 2024. "Epidemiological data of an influenza A/H5N1 outbreak in elephant seals in Argentina indicates mammal-to-mammal transmission," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Thomas Rawson & Christian Morgenstern & Edward S. Knock & Joseph Hicks & Anh Pham & Guillaume Morel & Aurelio Cabezas Murillo & Michael W. Sanderson & Giovanni Forchini & Richard FitzJohn & Katharina , 2025. "A mathematical model of H5N1 influenza transmission in US dairy cattle," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    3. Hui Yang & Yurui Dong & Ying Bian & Nuo Xu & Yuwei Wu & Fan Yang & Yinping Du & Tao Qin & Sujuan Chen & Daxin Peng & Xiufan Liu, 2022. "The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. repec:plo:pone00:0001790 is not listed on IDEAS
    5. Xin-Lou Li & Kun Liu & Hong-Wu Yao & Ye Sun & Wan-Jun Chen & Ruo-Xi Sun & Sake J. De Vlas & Li-Qun Fang & Wu-Chun Cao, 2015. "Highly Pathogenic Avian Influenza H5N1 in Mainland China," IJERPH, MDPI, vol. 12(5), pages 1-20, May.
    6. Zhijie Zhang & Dongmei Chen & Yue Chen & Bo Wang & Yi Hu & Jie Gao & Liqian Sun & Rui Li & Chenglong Xiong, 2014. "Evaluating the Impact of Environmental Temperature on Global Highly Pathogenic Avian Influenza (HPAI) H5N1 Outbreaks in Domestic Poultry," IJERPH, MDPI, vol. 11(6), pages 1-12, June.
    7. Ore Koren & Jessica Steinberg & Amit Hagar, 2024. "Meat production and zoonotic disease outbreaks in Asia," Australian Journal of Agricultural and Resource Economics, Australian Agricultural and Resource Economics Society, vol. 68(3), pages 567-586, July.
    8. Qian Niu & Zhiwen Jiang & Lifang Wang & Xiang Ji & Guy Baele & Ying Qin & Liyan Lin & Alexander Lai & Ye Chen & Michael Veit & Shuo Su, 2025. "Prevention and control of avian influenza virus: Recent advances in diagnostic technologies and surveillance strategies," Nature Communications, Nature, vol. 16(1), pages 1-7, December.
    9. Chaiban, Celia & Biscio, Christophe & Thanapongtharm, Weerapong & Tildesley, Michael & Xiao, Xiangming & Robinson, Timothy P. & Vanwambeke, Sophie O. & Gilbert, Marius, 2019. "Point pattern simulation modelling of extensive and intensive chicken farming in Thailand: Accounting for clustering and landscape characteristics," Agricultural Systems, Elsevier, vol. 173(C), pages 335-344.
    10. Marina R. Good & Monica L. Fernández-Quintero & Wei Ji & Alesandra J. Rodriguez & Julianna Han & Andrew B. Ward & Jenna J. Guthmiller, 2024. "A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    11. Mohammed Nooruzzaman & Lina M. Covaleda & Pablo Sebastian Britto Oliveira & Nicole H. Martin & Katherine J. Koebel & Renata Ivanek & Samuel D. Alcaine & Diego G. Diel, 2025. "Thermal inactivation spectrum of influenza A H5N1 virus in raw milk," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    12. Jenna Schafers & Caroline J. Warren & Jiayun Yang & Junsen Zhang & Sarah J. Cole & Jayne Cooper & Karolina Drewek & B. Reddy Kolli & Natalie McGinn & Mehnaz Qureshi & Scott M. Reid & Thomas P. Peacock, 2025. "Pasteurisation temperatures effectively inactivate influenza A viruses in milk," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    13. Qingxia Zhang & Dingcheng Wang, 2014. "Antiviral Prophylaxis and Isolation for the Control of Pandemic Influenza," IJERPH, MDPI, vol. 11(8), pages 1-23, July.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58504-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.