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Live attenuated influenza vaccine with low proportions of defective interfering particles elicits robust immunogenicity and cross-protection

Author

Listed:
  • Min Wu

    (Jilin University)

  • Peihan Wang

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Likun Wang

    (Jilin University)

  • Cuidan Li

    (China National Center for Bioinformation
    Chinese Academy of Sciences)

  • Rui Sheng

    (Jilin University)

  • Hanwen Dong

    (Jilin University)

  • Xiaoshu Fu

    (Jilin University)

  • Entong Zhou

    (Jilin University)

  • Chun Zhang

    (Changchun BCHT Biotechnology Co.)

  • Tianyi Lu

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhengyang Jin

    (Jilin University)

  • Jiaqi Qin

    (Jilin University)

  • Yuxuan Miao

    (Jilin University)

  • Liya Yue

    (China National Center for Bioinformation
    Chinese Academy of Sciences)

  • Dong Pan

    (Changchun BCHT Biotechnology Co.)

  • Chao Li

    (Changchun BCHT Biotechnology Co.)

  • Chongyang Liang

    (Jilin University)

  • Irina Kiseleva

    (Institute of Experimental Medicine)

  • Larisa Rudenko

    (Institute of Experimental Medicine)

  • Chunlai Jiang

    (Jilin University
    Jilin University)

  • Fei Chen

    (China National Center for Bioinformation
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    The First Affiliated Hospital of Xinjiang Medical University)

  • Weiheng Su

    (Jilin University
    Jilin University)

Abstract

Commercial live attenuated influenza vaccines (LAIVs) usually contain a high proportion of defective interfering particles (DIPs). Given that LAIVs are not sufficiently protective worldwide, the potential to enhance their efficacy by reducing the proportion of DIPs remains largely unknown. In this study, a prepared H3N2 cold-adapted LAIV with a low proportion of DIPs exhibits delayed yet improved replication in the upper respiratory tract of mice. The low DIPs LAIV induces an increase in goblet cells, microfold cells, and neutrophils, along with enhanced antigen presentation by dendritic cells. Compared to the commercially sourced high DIPs LAIV, the low DIPs LAIV elicits enhanced mucosal and humoral immune responses, facilitates cross-neutralization in mice, and provides complete protection against lethal challenges with H3N2, H1N1 or H1N1pdm09 strains. This study offers insights into optimizing commercial LAIVs and replicative RNA virus-based vaccines by controlling DIPs.

Suggested Citation

  • Min Wu & Peihan Wang & Likun Wang & Cuidan Li & Rui Sheng & Hanwen Dong & Xiaoshu Fu & Entong Zhou & Chun Zhang & Tianyi Lu & Zhengyang Jin & Jiaqi Qin & Yuxuan Miao & Liya Yue & Dong Pan & Chao Li & , 2025. "Live attenuated influenza vaccine with low proportions of defective interfering particles elicits robust immunogenicity and cross-protection," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64651-0
    DOI: 10.1038/s41467-025-64651-0
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    References listed on IDEAS

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    1. Katrina B. Mar & Nicholas R. Rinkenberger & Ian N. Boys & Jennifer L. Eitson & Matthew B. McDougal & R. Blake Richardson & John W. Schoggins, 2018. "LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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