Live attenuated influenza vaccine with low proportions of defective interfering particles elicits robust immunogenicity and cross-protection
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.
Authors
- Min Wu (ORCID: https://orcid.org/0000-0003-2974-9368)
- Zhengyang Jin
- Rui Sheng
- Xiaoshu Fu
- Irina Kiseleva (ORCID: https://orcid.org/0000-0002-3892-9873)
- Tianyi Lu (ORCID: https://orcid.org/0000-0001-8410-9051)
- Weiheng Su (ORCID: https://orcid.org/0000-0002-9577-7423)
- Liya Yue (ORCID: https://orcid.org/0000-0002-5752-6914)
- Jiaqi Qin (ORCID: https://orcid.org/0000-0002-8722-6533)
- Larisa Rudenko (ORCID: https://orcid.org/0000-0002-0107-9959)
- Entong Zhou
- Cuidan Li (ORCID: https://orcid.org/0000-0002-8430-1155)
- Dong Pan (ORCID: https://orcid.org/0000-0003-4410-9123)
- Chao Li (ORCID: https://orcid.org/0000-0002-1950-0190)
- Fei Chen (ORCID: https://orcid.org/0000-0003-3895-6318)
- Chun Zhang (ORCID: https://orcid.org/0000-0002-4646-1879)
- Likun Wang (ORCID: https://orcid.org/0000-0002-0298-8249)
- Yi Miao (ORCID: https://orcid.org/0000-0003-2542-8663)
- Chunlai Jiang (ORCID: https://orcid.org/0000-0002-6588-3997)
- Peihan Wang (ORCID: https://orcid.org/0000-0001-6701-6179)
- Hanwen Dong
- C. Jason Liang (ORCID: https://orcid.org/0000-0002-4832-6590)
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Xinjiang Medical University (CN)
- Jinan University (CN)
- Jilin University (CN)
- Chinese Academy of Sciences (CN)
- Beijing Institute of Genomics (CN)
- First Affiliated Hospital of Xinjiang Medical University (CN)
- China National Biotechnology (China) (CN)
- Institute of Experimental Medicine (RU)
- Ministry of Education (KN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-31
- DOI
- https://doi.org/10.1038/s41467-025-64651-0
- Citations
- 1
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- People's Government of Jilin Province