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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月31日

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  • 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,
  • Chongyang Liang,
  • Irina Kiseleva,
  • Larisa Rudenko,
  • Chunlai Jiang,
  • Fei Chen,
  • Weiheng Su

摘要

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.