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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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03122-6 |
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| author | Yongqiang Zhao Jia Liu Chun Peng Shuangshuang Guo Bo Wang Longping Chen Yating Wang Haiwen Tang Liming Liu Qi Pan Shiren Li Jingyu Wang Dongni Yang Enqi Du |
| author_facet | Yongqiang Zhao Jia Liu Chun Peng Shuangshuang Guo Bo Wang Longping Chen Yating Wang Haiwen Tang Liming Liu Qi Pan Shiren Li Jingyu Wang Dongni Yang Enqi Du |
| author_sort | Yongqiang Zhao |
| collection | DOAJ |
| description | 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 |
| format | Article |
| id | doaj-art-22f6612c1af74e3bb3f8ce03c4f9c188 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-22f6612c1af74e3bb3f8ce03c4f9c1882025-02-09T12:53:04ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112110.1186/s12951-025-03122-6Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccineYongqiang Zhao0Jia Liu1Chun Peng2Shuangshuang Guo3Bo Wang4Longping Chen5Yating Wang6Haiwen Tang7Liming Liu8Qi Pan9Shiren Li10Jingyu Wang11Dongni Yang12Enqi Du13College of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityChengdu NanoVAX Biotechnology Co., Ltd.Yangling Carey Biotechnology Co., Ltd.Yangling Carey Biotechnology Co., Ltd.Yangling Carey Biotechnology Co., Ltd.College of Veterinary Medicine, Northwest A&F UniversityChengdu NanoVAX Biotechnology Co., Ltd.Nanjing JSIAMA Biopharmaceuticals Ltd.Nanjing JSIAMA Biopharmaceuticals Ltd.Chengdu NanoVAX Biotechnology Co., Ltd.College of Veterinary Medicine, Northwest A&F UniversityChengdu NanoVAX Biotechnology Co., Ltd.College of Veterinary Medicine, Northwest A&F UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12951-025-03122-6Influenza virusNanoparticle vaccineUniversal influenza vaccineCross-protection |
| spellingShingle | Yongqiang Zhao Jia Liu Chun Peng Shuangshuang Guo Bo Wang Longping Chen Yating Wang Haiwen Tang Liming Liu Qi Pan Shiren Li Jingyu Wang Dongni Yang Enqi Du Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine Journal of Nanobiotechnology Influenza virus Nanoparticle vaccine Universal influenza vaccine Cross-protection |
| title | Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine |
| title_full | Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine |
| title_fullStr | Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine |
| title_full_unstemmed | Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine |
| title_short | Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine |
| title_sort | cross protection against homo and heterologous influenza viruses via intranasal administration of an ha chimeric multiepitope nanoparticle vaccine |
| topic | Influenza virus Nanoparticle vaccine Universal influenza vaccine Cross-protection |
| url | https://doi.org/10.1186/s12951-025-03122-6 |
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