{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:35:33Z","timestamp":1774542933143,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The nanoparticles demonstrated excellent stability (PDI&amp;lt;0.3 for 7 days), efficient pDNA encapsulation (confirmed by UV), and sustained release (93.14% \u00b1 4.12% at 72 h). DC2.4 cells uptake assays revealed significant antigen-presenting cell internalization (p&amp;lt;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&amp;lt;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&amp;lt;0.05), demonstrating robust cross-subtype protection against lethal infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study establishes a significant conceptual framework for advancing the development of DNA-based influenza vaccines with sustained protective efficacy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1572618","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:10:42Z","timestamp":1749640242000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Silica-calcium phosphate nanoparticles delivering recombinant influenza hemagglutinin DNA can induce long-lasting T cell immune cross-protection in 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