tetano
Editor, Senior Moderator
J Nanobiotechnology
. 2025 Feb 4;23(1):77.
doi: 10.1186/s12951-025-03122-6. Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine
Yongqiang Zhao[SUP] 1 [/SUP], Jia Liu[SUP] 1 [/SUP], Chun Peng[SUP] 2 [/SUP], Shuangshuang Guo[SUP] 3 [/SUP], Bo Wang[SUP] 3 [/SUP], Longping Chen[SUP] 3 [/SUP], Yating Wang[SUP] 1 [/SUP], Haiwen Tang[SUP] 2 [/SUP], Liming Liu[SUP] 4 [/SUP], Qi Pan[SUP] 4 [/SUP], Shiren Li[SUP] 2 [/SUP], Jingyu Wang[SUP] 1 [/SUP], Dongni Yang[SUP] 5 [/SUP], Enqi Du[SUP] 6 7 [/SUP]
Affiliations
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.
Keywords: Cross-protection; Influenza virus; Nanoparticle vaccine; Universal influenza vaccine.
. 2025 Feb 4;23(1):77.
doi: 10.1186/s12951-025-03122-6. Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine
Yongqiang Zhao[SUP] 1 [/SUP], Jia Liu[SUP] 1 [/SUP], Chun Peng[SUP] 2 [/SUP], Shuangshuang Guo[SUP] 3 [/SUP], Bo Wang[SUP] 3 [/SUP], Longping Chen[SUP] 3 [/SUP], Yating Wang[SUP] 1 [/SUP], Haiwen Tang[SUP] 2 [/SUP], Liming Liu[SUP] 4 [/SUP], Qi Pan[SUP] 4 [/SUP], Shiren Li[SUP] 2 [/SUP], Jingyu Wang[SUP] 1 [/SUP], Dongni Yang[SUP] 5 [/SUP], Enqi Du[SUP] 6 7 [/SUP]
Affiliations
- PMID: 39905416
- PMCID: PMC11792681
- DOI: 10.1186/s12951-025-03122-6
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.
Keywords: Cross-protection; Influenza virus; Nanoparticle vaccine; Universal influenza vaccine.