tetano
Editor, Senior Moderator
Front Immunol
. 2025 Jun 3:16:1572618.
doi: 10.3389/fimmu.2025.1572618. eCollection 2025. Silica-calcium phosphate nanoparticles delivering recombinant influenza hemagglutinin DNA can induce long-lasting T cell immune cross-protection in mice
Xiaoxi Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Qingyu Wang[SUP] #[/SUP][SUP] 1 [/SUP], Yuhua Shi[SUP] 1 [/SUP], Li Zhan[SUP] 1 [/SUP], Lipeng Xu[SUP] 1 [/SUP], Jiaru Hui[SUP] 1 [/SUP], Kunpeng Xie[SUP] 1 [/SUP], Chenxi Li[SUP] 1 [/SUP], Chunjiang Li[SUP] 1 3 [/SUP], Weiheng Su[SUP] 1 [/SUP], Xianbin Cheng[SUP] 4 [/SUP], Yaming Shan[SUP] 1 5 [/SUP]
Affiliations
Introduction: Vaccination remains one of the key tools to prevent influenza pandemic. The influenza vaccine induces durable cross-subtype protection through T-cell immunity, demonstrating significant future potential. DNA vaccines are effective in sustaining the expression of antigens, which can trigger T-cell immune responses. Calcium phosphate nanoparticles can also induce T-cell immune responses by assisting in the activation of DC cells by antigens.
Methods: This study developed silica-coated calcium phosphate nanoparticles (226 nm) encapsulating influenza hemagglutinin plasmids (pHAF/pHAG) via polyethyleneimine adsorption. Further analysis of its bioactivity was conducted through experiments.
Results: The nanoparticles demonstrated excellent stability (PDI<0.3 for 7 days), efficient pDNA encapsulation (confirmed by UV), and sustained release (93.14% ± 4.12% at 72 h). DC2.4 cells uptake assays revealed significant antigen-presenting cell internalization (p<0.0001). BALB/c mice were immunized subcutaneously using a prime-boost-boost regimen at two-week intervals. Splenocyte analysis revealed sustained elevation of CD4+ and CD8+ T cell proportions (p<0.05) at 12 weeks post-immunization, suggesting nanoparticle-induced durable T cell immunity. Post-immunization challenge with heterologous H3N2 revealed striking protection: SCPs/pHAF conferred 100% survival, while SCPs/pHAG achieved 66% survival. Notably, SCPs/pDNA immunization significantly reduced lung viral titers versus controls (p<0.05), demonstrating robust cross-subtype protection against lethal infection.
Discussion: This study establishes a significant conceptual framework for advancing the development of DNA-based influenza vaccines with sustained protective efficacy.
Keywords: T-cell immunity; hemagglutinin; influenza virus; nanoparticles; subunit vaccine.
. 2025 Jun 3:16:1572618.
doi: 10.3389/fimmu.2025.1572618. eCollection 2025. Silica-calcium phosphate nanoparticles delivering recombinant influenza hemagglutinin DNA can induce long-lasting T cell immune cross-protection in mice
Xiaoxi Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Qingyu Wang[SUP] #[/SUP][SUP] 1 [/SUP], Yuhua Shi[SUP] 1 [/SUP], Li Zhan[SUP] 1 [/SUP], Lipeng Xu[SUP] 1 [/SUP], Jiaru Hui[SUP] 1 [/SUP], Kunpeng Xie[SUP] 1 [/SUP], Chenxi Li[SUP] 1 [/SUP], Chunjiang Li[SUP] 1 3 [/SUP], Weiheng Su[SUP] 1 [/SUP], Xianbin Cheng[SUP] 4 [/SUP], Yaming Shan[SUP] 1 5 [/SUP]
Affiliations
- PMID: 40568589
- PMCID: PMC12188357
- DOI: 10.3389/fimmu.2025.1572618
Introduction: Vaccination remains one of the key tools to prevent influenza pandemic. The influenza vaccine induces durable cross-subtype protection through T-cell immunity, demonstrating significant future potential. DNA vaccines are effective in sustaining the expression of antigens, which can trigger T-cell immune responses. Calcium phosphate nanoparticles can also induce T-cell immune responses by assisting in the activation of DC cells by antigens.
Methods: This study developed silica-coated calcium phosphate nanoparticles (226 nm) encapsulating influenza hemagglutinin plasmids (pHAF/pHAG) via polyethyleneimine adsorption. Further analysis of its bioactivity was conducted through experiments.
Results: The nanoparticles demonstrated excellent stability (PDI<0.3 for 7 days), efficient pDNA encapsulation (confirmed by UV), and sustained release (93.14% ± 4.12% at 72 h). DC2.4 cells uptake assays revealed significant antigen-presenting cell internalization (p<0.0001). BALB/c mice were immunized subcutaneously using a prime-boost-boost regimen at two-week intervals. Splenocyte analysis revealed sustained elevation of CD4+ and CD8+ T cell proportions (p<0.05) at 12 weeks post-immunization, suggesting nanoparticle-induced durable T cell immunity. Post-immunization challenge with heterologous H3N2 revealed striking protection: SCPs/pHAF conferred 100% survival, while SCPs/pHAG achieved 66% survival. Notably, SCPs/pDNA immunization significantly reduced lung viral titers versus controls (p<0.05), demonstrating robust cross-subtype protection against lethal infection.
Discussion: This study establishes a significant conceptual framework for advancing the development of DNA-based influenza vaccines with sustained protective efficacy.
Keywords: T-cell immunity; hemagglutinin; influenza virus; nanoparticles; subunit vaccine.