Adjuvant-free, self−assembling ferritin nanoparticle vaccine coupled with influenza virus hemagglutinin protein carrying M1 and PADRE epitopes elicits cross-protective immune responses

作者：Yongqiang Zhao, Shuangshuang Guo, Jia Liu, Yating Wang, Bo Wang, Chun Peng, Enqi Du · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1519866 · 被引用次数：8 · 研究领域：Influenza Virus Research Studies、interferon and immune responses、vaccines and immunoinformatics approaches

Introduction: Influenza viruses pose a significant threat to global public health. Several influenza pandemic outbreaks have had serious economic and public health implications. Current influenza virus vaccines generally provide strain-specific protection and must be rapidly produced annually to match the circulating viruses. Developing influenza vaccines that confer protection against a broad range of viruses will have a positive impact on public health. In this study, we aimed to develop a ferritin-based influenza nanoparticle vaccine with a broad protective spectrum to enhance the immune response against diverse influenza viruses. Results: ferritin, which consists of the ectodomain of hemagglutinin of the H3N2 virus and three tandem highly conserved influenza M1 epitopes fused with the universal helper T-cell epitope PADRE, named HMP-NP. HMP-NPs were expressed in a soluble form in the baculovirus-insect cell system and self-assembled into homogeneous nanoparticles. Animal immunization studies showed that the HMP-NP nanovaccine elicited 4-fold higher haemagglutination inhibition (HAI) titers than inactivated influenza vaccine. And neutralization titers induced by HMP-NPs against the H3N2 virus and heterologous strains of the H1N1 and H9N2 viruses were ~8, 12.4 and 16 times higher than inactivated influenza vaccine, respectively. Meanwhile, we also observed that the number of IFN-γ- and IL-4-secreting cells induced by HMP-NPs were ~2.5 times higher than inactivated influenza...