ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1572618
This article is part of the Research TopicAnimal-borne viral disease: Pathogenesis, Innate immunity, Acquired immunity, and Novel vaccine developmentView all 10 articles
Silica-calcium phosphate nanoparticles delivering recombinant influenza hemagglutinin DNA can induce long-lasting T cell immune cross-protection in mice
Provisionally accepted
Xiaoxi Liu1
Qingyu Wang1Yuhua Shi1Li Zhan1Lipeng Xu1Jiaru Hui1Kunpeng Xie1Chenxi Li1Chunjiang Li1
Weiheng Su1
Xianbin Cheng2*
Yaming Shan1- 1Jilin University, Changchun, Hebei Province, China
- 2Second Affiliated Hospital of Jilin University, Changchun, China
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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.This study developed silica-coated calcium phosphate nanoparticles (226 nm) encapsulating influenza hemagglutinin plasmids (pHAF/pHAG) via polyethyleneimine adsorption. 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 twoweek 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. This study establishes a significant conceptual framework for advancing the development of DNAbased influenza vaccines with sustained protective efficacy.
Keywords: Influenza Virus, hemagglutinin, subunit vaccine, Nanoparticles, T-cell immunity
Received: 07 Feb 2025; Accepted: 13 May 2025.
Copyright: © 2025 Liu, Wang, Shi, Zhan, Xu, Hui, Xie, Li, Li, Su, Cheng and Shan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xianbin Cheng, Second Affiliated Hospital of Jilin University, Changchun, China
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