Polyethylenimine-based micro/nanoparticles as vaccine adjuvants

Abstract

Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses. Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades. However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants. In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines. In addition, we sum up the proof of their in vivo and clinical applications. We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses.

Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis

“…Having established several features that improve the IONV vaccination efficacy, we considered whether other biocompatible nanoparticles previously used for development of nanovaccines such as gold nanoparticles (AuNPs) ( Almeida et al., 2014 ) might elicit similar antitumor efficacy. Studies have highlighted the potential of polyethylenimine (PEI) ( Shen et al., 2017 ; Liang et al., 2018 ), one of the well-studied cationic polymers used as a transfection reagent for decades, for vaccine development. The mechanisms for the intrinsic immunoactivation function of PEI are diverse and include the triggering of “danger signals” in antigen-presenting cells and the ability to elicit ROS ( Shen et al., 2017 ).…”

“…Studies have highlighted the potential of polyethylenimine (PEI) ( Shen et al., 2017 ; Liang et al., 2018 ), one of the well-studied cationic polymers used as a transfection reagent for decades, for vaccine development. The mechanisms for the intrinsic immunoactivation function of PEI are diverse and include the triggering of “danger signals” in antigen-presenting cells and the ability to elicit ROS ( Shen et al., 2017 ). We prepared AuNPs coated with PEI ( Garaikoetxea Arguinzoniz et al., 2015 ) and by exploiting its positive charge, we developed PEI-modified AuNPs suitable for forming complexes with the anionic polyIC-R837 adjuvant.…”

Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies

“…However, it provides lower transfection efficiency due to its inability to form stable structures with DNA, and protect it from enzyme attack and exposure to harsh biological environments. In order to improve the transfection efficiency of PEI NPs while minimizing toxicity, modification strategies can be applied including conjugation of high MW weight branched PEIs with polysaccharides, hydrophilic polymers, disulfide bridges, and lipid moieties [56]. For the purpose of DNA vaccination specifically, PEI has been used to encapsulate DNA encoding hemagglutinin (HA) from influenza A H5N1 for intranasal immunization which generated high levels of HA-specific IgG A antibodies and protective humoral and cell-mediated immunity against H5N1 challenge in mouse models [57].…”

Ultrathin polyethyleneimine (PEI) films for culturing of the human mesenchymal stromal cells (hMSCs)

“…Various modifi cations of PEI are used as adjuvants enhancing immune response of a body against action of a vaccine [12].…”