Polymeric particles in vaccine delivery

Rice‐Ficht, Allison C.; Arenas-Gamboa, Ángela M.; Kahl-McDonagh, Melissa; Ficht, Thomas A.

doi:10.1016/j.mib.2009.12.001

Cited by 181 publications

(112 citation statements)

References 61 publications

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“…Since the size and charge of polymer-DNA complexes have been shown to be important factors that affect the kinetics of cellular uptake and the mode of immune stimulation [25], the size and charge of the PEI-DNA complexes were measured. Five PEI polymers were complexed to plasmid DNA at an N/P ratio of 7.5.…”

Section: Resultsmentioning

confidence: 99%

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

et al. 2012

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The utility of plasmid DNA as an immunogen has been limited by its weak immunogenicity. In the present study, we evaluated the ability of a family of linear polyethylenimine (PEI) polymers, complexed to plasmid DNA, to augment DNA expression in vivo and to enhance antigen-specific adaptive immune responses. We showed that four of five structurally different PEIs that we evaluated increased in vivo DNA expression 20-to 400-fold, and enhanced DNA-induced epitope-specific CD8 IntroductionDNA vaccine constructs have been evaluated and are being tested in a number of human clinical trials for generating immunity to many types of diseases, including infectious, cancer, allergic, and autoimmune diseases [1,2]. In addition, the use of DNA vaccinesCorrespondence: Dr. Evita V. Grant e-mail: evita.grant@gmail.com has proven effective in some current veterinary products such as a vaccine against infectious hematopoietic necrosis virus for salmon [3], melanoma immunotherapeutic vaccine for dogs [4] and a vaccine against the West Nile Virus for horses [5]. Unfortunately, the immunogenicity of plasmid DNA in humans has proven to be modest in comparison with the immunogenicity observed in other species of microbial expression vectors. Consequently, efforts are being made to increase the immunogenicity of DNA vaccine constructs. Strategies have been developed to increase plasmid DNA expression via codon modification [6], the use of enhanced promoters [7] and the use of microbial transcriptional C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 2938 Evita V. Grant et al. Eur. J. Immunol. 2012. 42: 2937-2948 control elements [8]. Since plasmid DNA has poor in vivo transfection efficiency, a number of formulations of plasmid DNA have been evaluated to protect DNA from degradation and to enhance transfection efficiency [9][10][11]. The "gene gun" technology [12] was developed to enhance DNA delivery and immunogenicity. Furthermore, immunomodulation strategies have been evaluated for their ability to enhance DNA immunogenicity [13][14][15]. The synthetic polycationic polymer polyethylenimine (PEI), consisting of chains of ethylenimine units-CH 2 CH 2 NH-, has become the gold standard for enhancing the in vivo expression of administered genes [16,17]. PEI is superior to other nonmicrobial transfection agents because of its ability to protect DNA from degradation [18], to escape intracellular endosomal lysis [19] and to efficiently deliver DNA into the nucleus of cells [20]. Formulation with PEI polymers has been employed in DNA-and siRNAbased immunotherapy against cancer [21,22] and in vaccination studies targeting different infectious agents [10,23,24].In the present study, we have evaluated the physicochemical characteristics of a series of PEI polymers and have assessed associations between particular characteristics of these polymers and their ability to facilitate in vivo DNA expression and enhanced adaptive immune responses. Moreover, we have examined plasmid DNA constructs formulated with these various PEI...

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Section: Resultsmentioning

confidence: 99%

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

et al. 2012

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“…However, the extended release of antigen as well as induction of innate and adaptive immune response are concerns. 18,19 For this study, we have chosen anti-CD205 monoclonal Ab (MAb) to target CD205 receptor on DCs because it is an extensively studied receptor for antigen delivery. [20][21][22] The formulations were designed using capped (ester) and uncapped (COOH) PLGA, both offering low and high viscosity grades.…”

Section: Introductionmentioning

confidence: 99%

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

Jahan¹,

Sadat²,

Haddadi³

2018

IJN

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The aim of this research was to develop a targeted antigen–adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method. Targeted NPs were obtained through ligand incorporation via physical adsorption or chemical conjugation process. Intracellular uptake of the NPs and the maturation of DCs were evaluated with flow cytometry. Remarkably, the developed delivery system had suitable physicochemical properties, such as particle size, surface charge, OV encapsulation efficiency, biphasic OV release pattern, and safety profile. The ligand modified formulations had higher targeting efficiency than the non-tailored NPs. This was also evident when the targeted formulations expressed comparatively higher fold increase in surface activation markers such as CD40, CD86, and major histocompatibility complex class II molecules. The maturation of DCs was further confirmed through secretion of extracellular cytokines compared to control cells in the DC microenvironment. Physicochemical characterization of NPs was performed based on the polymer end groups, their viscosities, and ligand-NP bonding type. In conclusion, the DC stimulatory response was integrated to develop a relationship between the NP structure and desired immune response. Therefore, the present study narrates a comparative evaluation of some selected parameters to choose a suitable formulation useful for in vivo cancer immunotherapy.

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“…19 The past decade has seen important developments in the use of nanotechnology in the field of vaccine adjuvants and carrier vehicles, especially polymeric materials in the nano-and microranges. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] These studies hold great promise to elicit complex immune responses from all branches of immunity for effective and safe vaccination against major infections that have escaped effective vaccination.…”

mentioning

confidence: 99%

Fabrication of nanoadjuvant with poly-e-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity

Prashant

Bhat

Srivastava

et al. 2014

IJN

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Purpose The aim of the study was to load a model antigen, tetanus toxoid (TT), in poly-ε-caprolactone nanoparticles (PCL NPs) of two size ranges, ie, mean 61.2 nm (small) and 467.6 nm (large), and study its effect on macrophage polarization as well as antigen presentation in human monocyte-derived macrophages in vitro, along with humoral and cell-mediated immune (CMI) response generated in Swiss albino mice following immunization with the TT-loaded NPs. Materials and methods PCL NPs were synthesized by solvent evaporation. The antigen-loaded PCL NPs were characterized for size, zeta potential, and protein-release kinetics. Swiss albino mice were immunized with the antigen-loaded PCL NPs. Flow cytometry was used to quantify interferon-γ- and interleukin-4-secreting cluster of differentiation (CD)4 + and CD8 + T cells in the spleen, and enzyme-linked immunosorbent assay was used to quantify anti-TT antibody levels in the serum of immunized mice. Results Small PCL NPs generated an M1/M2 type polarization of human blood monocyte-derived macrophages and T helper (Th)1/Th2 polarization of autologous CD4 + T cells. Efficient CD8 + T-cell responses were also elicited. Large PCL NPs failed to cause any type of macrophage polarization. They did not elicit efficient CD8 + T-cell responses. Conclusion TT-loaded small PCL NPs were able to generate persistent and strong CMI and humoral responses against TT 2 months after single injection in mice without booster dose. This biodegradable nanoadjuvant system may help to develop single-shot immunization for prolonged immunity without booster doses. The capability of enhanced CMI response may have high translational potential for immunization against intracellular infection.

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Polymeric particles in vaccine delivery

Cited by 181 publications

References 61 publications

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine

Fabrication of nanoadjuvant with poly-e-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity

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