Dendrigraft poly-L-lysines delivery of DNA vaccine effectively enhances the immunogenic responses against H9N2 avian influenza virus infection in chickens

Zhao, Kai; Rong, Guangyu; Teng, Quincy; Li, Xuesong; Lan, Hailing; Yu, Lu; Yu, Shuang; Jin, Zheng; Chen, Guangping; Li, Zejun

doi:10.1016/j.nano.2020.102209

Cited by 14 publications

(18 citation statements)

References 45 publications

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“…Zhao et al encapsulated the HA gene of H9N2 influenza virus plasmid DNA (pDNA) into dendrigraft poly- L -lysines (DGLs) via electrostatic interactions. After intramuscular injection, DGLs prevented pDNA degradation, assisted pDNA escape from endosomes, promoted antigen presentation, and induced effective cellular and humoral immune responses, thereby demonstrating that DGLs were good non-viral nucleic acid vaccine delivery carriers 32 . To increase positive charge densities in the polymer structure, considerable attention has been paid to the development of highly branched poly(amino acid)s as gene delivery vectors 33 , which will also show great potential in vaccine delivery.…”

Section: Types Of Polymer Carriers For Nucleic Acid Vaccine Deliverymentioning

confidence: 96%

Advances in the polymeric delivery of nucleic acid vaccines

et al. 2022

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Nucleic acid vaccines, especially messenger RNA (mRNA) vaccines, display unique benefits in the current COVID-19 pandemic. The application of polymeric materials as delivery carriers has greatly promoted nucleic acid vaccine as a promising prophylactic and therapeutic strategy. The inherent properties of polymeric materials render nucleic acid vaccines with excellent in vivo stability, enhanced biosafety, specific cellular uptake, endolysosomal escape, and promoted antigen expression. Although polymeric delivery of nucleic acid vaccines has progressed significantly in the past decades, clinical translation of polymer-gene vaccine systems still faces insurmountable challenges. This review summarizes the diverse polymers and their characterizations and representative formulations for nucleic acid vaccine delivery. We also discussed existing problems, coping strategies, and prospect relevant to applications of nucleic acid vaccines and polymeric carriers. This review highlights the rational design and development of polymeric vaccine delivery systems towards meeting the goals of defending serious or emerging diseases.

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Section: Types Of Polymer Carriers For Nucleic Acid Vaccine Deliverymentioning

confidence: 96%

Advances in the polymeric delivery of nucleic acid vaccines

et al. 2022

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“…In vitro cytotoxicity of Lipofectin and phage particles was evaluated using the Cell Counting Kit-8 (CCK-8) reagent (Dojindo Laboratories, Japan) according to the manufacturer's instructions. Based on the protocol described by Zhao et al (26), HEK293T cells were seeded in a 96 well plate at a density of 1×10 4 cells per well and incubated at 37°C in a 5% CO 2 humidified atmosphere for 24 h. Subsequently, the medium was replaced by fresh Dulbecco's Modified Eagle Medium (DMEM) mixed with 0, 5, 10, 15 and 20 mL Lipofectin to a final volume of 100 mL or by 100 mL fresh DMEM containing a final concentration of 0, 5×10 8 , 1×10 9 , 5×10 9 and 1×10 10 pfu/mL phage particles. After a 4 h incubation, Lipofectin and phages were removed by a single wash, and cells were cultured for an additional 24-72 h. Thereafter, 10 mL of CCK-8 reagent was added and incubated for another 4 h. The absorbance at 450 nm was read with a microplate reader (iMark microplate reader, BIO-RAD).…”

Section: Evaluation Of the Cytotoxicity Of Lipofectin And Phage Parti...mentioning

confidence: 99%

Evaluation of dendritic cell-targeting T7 phages as a vehicle to deliver avian influenza virus H5 DNA vaccine in SPF chickens

et al. 2022

Front. Immunol.

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IntroductionThere is a growing demand for effective technologies for the delivery of antigen to antigen-presenting cells (APCs) and their immune-activation for the success of DNA vaccines. Therefore, dendritic cell (DC)-targeting T7 phages were used as a vehicle to deliver DNA vaccine.MethodsIn this study, a eukaryotic expression plasmid pEGFP-C1-HA2-AS containing the HA2 gene derived from the avian H5N1 virus and an anchor sequence (AS) gene required for the T7 phage packaging process was developed. To verify the feasibility of phage delivery, the plasmid encapsulated in DC-targeting phage capsid through the recognition of AS was evaluated both in vitro and in vivo. The pEGFP-C1-HA2-AS plasmid could evade digestion by DNase I by becoming encapsulated into the phage particles and efficiently expressed the HA2 antigen in DCs with the benefit of DC-targeting phages.ResultsFor chickens immunized with the DC-targeting phage 74 delivered DNA vaccine, the levels of IgY and IgA antibodies, the concentration of IFN-γ and IL-12 cytokines in serum, the proliferation of lymphocytes, and the percentage of CD4+/CD8+ T lymphocytes isolated from peripheral blood were significantly higher than chickens which were immunized with DNA vaccine that was delivered by non-DC-targeting phage or placebo (p<0.05). Phage 74 delivered one-fiftieth the amount of pEGFP-C1-HA2-AS plasmid compared to Lipofectin, however, a comparable humoral and cellular immune response was achieved. Although, the HA2 DNA vaccine delivered by the DC-targeting phage induced enhanced immune responses, the protection rate of virus challenge was not evaluated.ConclusionThis study provides a strategy for development of a novel avian influenza DNA vaccine and demonstrates the potential of DC-targeting phage as a DNA vaccine delivery vehicle.

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“…92 Colcom, a French start-up, has commercialized a dendrimer-like structure first discovered by Collet et al and known as "lysine dendrigrafts," which display primary amine functionalities along its backbone and surface ( Figure 11). [77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][94][95][96][97][98][99][100][101][102][103][104][105][106][127][128][129][130][131][132][133][134][135][136][137][138] Lysine dendrigrafts are primarily utilized for drug 89 and gene delivery. 107 but have also been investigated for their potential as a coagulant, 108 imaging agent, 95 and substrates for tissue engineering.…”

Section: Hydrophilic Ifdsmentioning

confidence: 99%

Synthesis, structure, and function of internally functionalized dendrimers

Smith

Gorman

Menegatti

2020

Journal of Polymer Science

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The past three decades have witnessed an exponential increase in the structural diversity and applications of dendrimers, spanning across drug delivery and diagnostics, protein, and enzyme mimicry, solubility enhancement, coatings, light harvesting, and catalysis. The dendrimer community has recently focused on internally functionalized dendrimers (IFDs) owing to their advanced design and functionality. The synthesis of IFDs relies on advanced orthogonal chemistries and/or (de)protection schemes, as well as careful purification to minimize polydispersity of composition and molecular weight. The studies published on IFDs, however, lay scattered across the chemical literature, and a comprehensive presentation of structural rationale, synthetic procedures, and technologically relevant applications is missing. To address this need, this review presents a comprehensive collection and discussion of all available studies on IFDs, detailing their methods of synthesis and their structure-function correlations. The wide variety of internal functionalities, including hydroxyl, amine, carboxylic acid, allyl, alkyne, and imidazole groups, enables myriad applications in biochemistry, chemical and biomedical engineering, and material science. Particular focus is given to IFDs that are amenable to modular synthetic strategies, which promote higher synthetic yield and scalability, and therefore possess stronger translational and commercial potential. As such, this review guides research groups pursuing the difficult task of IFD rational design and synthesis providing them a concise roadmap to their mission.

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Dendrigraft poly-L-lysines delivery of DNA vaccine effectively enhances the immunogenic responses against H9N2 avian influenza virus infection in chickens

Cited by 14 publications

References 45 publications

Advances in the polymeric delivery of nucleic acid vaccines

Advances in the polymeric delivery of nucleic acid vaccines

Evaluation of dendritic cell-targeting T7 phages as a vehicle to deliver avian influenza virus H5 DNA vaccine in SPF chickens

Synthesis, structure, and function of internally functionalized dendrimers

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