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

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 () and Weiheng Su ()
Additional contact information
Min Wu: Jilin University
Peihan Wang: China National Center for Bioinformation
Likun Wang: Jilin University
Cuidan Li: China National Center for Bioinformation
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
Zhengyang Jin: Jilin University
Jiaqi Qin: Jilin University
Yuxuan Miao: Jilin University
Liya Yue: China National Center for Bioinformation
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
Fei Chen: China National Center for Bioinformation
Weiheng Su: Jilin University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-64651-0

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