(26) However, the adjuvant effect on cross protection against variant strains has not been investigated. (26) The PEI-adjuvanted subunit H1N1 HA protein protected mice against homologous influenza virus infection.

(27) PEI failed to induce protective cellular responses, including cytotoxic T-lymphocyte (CTL), due to a lack of IFN-Оі cytokine induction. (25,26) However, PEI-induced immunity is Th2-dominant, like most other damage-associated molecular pattern (DAMP) adjuvants like aluminum hydroxide (Alum). Studies have indicated that PEI could potently increase the immunogenicity of DNA and protein vaccines. (25) The assembled PEIвЂ“protein nanoparticle fabrication process is more straightforward, facile, rapid, and protein friendly than most nanoparticle formulations.

(11) Optimally, effective influenza vaccines require comprehensive Th1 and Th2 immune responses.Д¬ationic polymer polyethylenimine (PEI) can electrostatically complex with many biological macromolecules, enabling precise loading of antigenвЂ“adjuvant combinations in nanoparticles. (9,10) Th1 responses facilitate more rapid recovery, particularly after distantly related heterologous viral challenges where cross-reactive neutralizing antibodies are rare. Subunit protein vaccination and live influenza virus infection generally induce different profiles of immune responsesв”ЂTh2-dominant antibody responses or Th1 cellular responses, respectively. Adjuvants can enhance and manipulate immune responses in both scope and scale, thus improving protection potency and breadth. Moreover, intranasally administered protein antigens are generally less immunogenic, necessitating adjuvants for highly efficient intranasal protein vaccines. (7,8) However, HA-induced immunity usually targets the immunodominant and variable HA head domain and is therefore strain specific. (5,6) Most experimental or licensed influenza recombinant protein vaccines focused on hemagglutinin (HA) as the primary immunogen. Recombinant protein vaccines have attracted enormous attention in influenza research due to their safety profile, rapid and egg-free production, and scalable manufacturing processes. Polycationic PEI nanoplatforms merit future development into mucosal vaccine systems. Thus, the PEI-HA/CpG nanoparticle is a potential cross-protective influenza vaccine candidate. PEI and CpG synergized these comprehensive immune responses. These immune responses did not decay over six months of observation postimmunization. PEI-HA/CpG nanoparticles also induced enhanced local and systemic cellular immune responses. In contrast to the Th2-biased, IgG1-dominant antibody response generated by PEI-HA nanoparticles, PEI-HA/CpG nanoparticles generated more robust and balanced IgG1/IgG2a antibody responses with augmented neutralization activity and Fc-mediated antibody-dependent cellular cytotoxicity (ADCC). The conserved HA stalk region induced substantial antibodies in the nanoparticle immunization groups. Our results revealed that the nanoparticles significantly enhanced HA immunogenicity, providing heterologous cross-protection. Here we fabricated PEI-hemagglutinin (HA) and PEI-HA/CpG nanoparticles and investigated their immune responses and protective efficacies with an i.n. Polycationic polyethylenimine (PEI) could form nanoscale complexes with negatively charged viral glycoproteins.

The intranasal (i.n.) route is an ideal vaccination approach for infectious respiratory diseases like influenza.

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