Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine
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 deve...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03122-6 |
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| Summary: | 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 |
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| ISSN: | 1477-3155 |