NDLI: Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine

Content Provider	Springer Nature : BioMed Central
Author	Zhao, Yongqiang Liu, Jia Peng, Chun Guo, Shuangshuang Wang, Bo Chen, Longping Wang, Yating Tang, Haiwen Liu, Liming Pan, Qi Li, Shiren Wang, Jingyu Yang, Dongni Du, Enqi
Abstract	Background Influenza A viruses (IAVs) cause seasonal influenza epidemics and pose significant threats to public health. However, seasonal influenza vaccines often elicit strain-specific immune responses and confer little protection against mismatched strains. There is an urgent need to develop universal influenza vaccines against emerging and potentially re-emerging influenza virus infections. Multiepitope vaccines combining multiple conserved epitopes can induce more robust and broader immune responses and provide a potential solution. Results Here, we demonstrated that an HA chimeric multiepitope nanoparticle vaccine, delivered intranasally conferred broad protection against challenges with various influenza viruses in mice. The nanoparticle vaccine co-expresses the ectodomain of haemagglutinin (H), three repeated highly conserved ectodomains of matrix protein 2 (M), and the M-cell-targeting ligand Co4B (C) in a baculovirus-insect cell system. These elements (C, H and M) were presented on the surface of self-assembling ferritin (f) in tandem to generate a nanoparticle denoted as CHM-f. Intranasal vaccination with CHM-f nanoparticles elicited robust humoral and cellular immune responses, conferring complete protection against a variety of IAVs, including the A/PR8/34 H1N1 strain, the swine flu H3N2 strain, the avian flu H5N8 strain, and H9N2. When CHM-f nanoparticles adjuvanted with CpG IAMA-002, the weight loss protective effect, cellular immune responses and mucosal IgA responses were significantly augmented. Compared with controls, mice immunized with CHM-f nanoparticles with or without CpG IAMA-002 showed significant reductions in weight loss, lung viral titres and pathological changes. Conclusions These results suggest that CHM-f nanoparticle with or without CpG IAMA-002 is a promising candidate as a universal influenza vaccine. Graphical Abstract
Related Links	https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-025-03122-6.pdf
Ending Page	21
Page Count	21
Starting Page	1
File Format	HTM / HTML
ISSN	14773155
DOI	10.1186/s12951-025-03122-6
Journal	Journal of Nanobiotechnology
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2025-02-04
Access Restriction	Open
Subject Keyword	Biotechnology Nanotechnology Molecular Medicine Influenza virus Nanoparticle vaccine Universal influenza vaccine Cross-protection
Content Type	Text
Resource Type	Article
Subject	Bioengineering Pharmaceutical Science Medicine Applied Microbiology and Biotechnology Biomedical Engineering Molecular Medicine Nanoscience and Nanotechnology
Journal Impact Factor	10.6/2023
5-Year Journal Impact Factor	11.4/2023

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