Nasal delivery of chitosan–DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice

Iqbal, Muhammad Farooq; Lin, Wei; Jabbal‐Gill, Inderjit; Davis, S.S.; Steward, M. W.; Illum, Lisbeth

doi:10.1016/s0264-410x(02)00662-x

Cited by 121 publications

(48 citation statements)

References 39 publications

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“…18,19 Consequently, chitosan has been used successfully for nasal delivery of vaccines. [20][21][22] Intradermal and intranasal immunization was found to induce a comparable peptide and virusspecific CTL responses. 20 Other studies show that chitosan nanoparticles can be used for oral immunization to induce a specific immune response.…”

Section: Introductionmentioning

confidence: 92%

“…[20][21][22] Intradermal and intranasal immunization was found to induce a comparable peptide and virusspecific CTL responses. 20 Other studies show that chitosan nanoparticles can be used for oral immunization to induce a specific immune response. 23,24 More recently, Ghendon et al 25 found chitosan to act as an adjuvant during immunization, as addition of chitosan to the antigen injected parentally resulted in a 4 or 6-10-fold increase in antibody titres after a single dose or with two doses in the case of IM immunization of mice.…”

Section: Introductionmentioning

confidence: 92%

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Chitosan–plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies

et al. 2009

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Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived growth factor-bb (PDGF-BB) and fibroblast growth factor-2 (FGF-2) are known to induce chemotaxis, proliferation, differentiation, and matrix synthesis, we investigated a non-viral means for gene delivery of these factors using the cationic polysaccharide chitosan. Chitosan is a polymer of glucosamine and N-acetylglucosamine, in which the percentage of the residues that are glucosamine is called the degree of deacetylation (DDA). The purpose of this study was to express PDGF-BB and FGF-2 genes in mice using chitosan-plasmid DNA nanoparticles for the controlled delivery of genetic material in a specific, efficient, and safe manner. PDGF-BB and FGF-2 genes were amplified from human tissues by RT-PCR. To increase the secretion of FGF-2, a recombinant 4sFGF-2 was constructed bearing eight amino-acid residues of the signal peptide of FGF-4. PCR products were inserted into the expression vector pVax1 to produce recombinant plasmids pVax1-4sFGF2 and pVax1-PDGF-BB, which were then injected into BALB/C mice in the format of polyelectrolyte nanocomplexes with specific chitosans of controlled DDA and molecular weight, including 92-10, 80-10, and 80-80 (DDA-number average molecular weight or M n in kDa). ELISA assays on mice sera showed that recombinant FGF-2 and PDGF-BB proteins were efficiently expressed and specific antibodies to these proteins could be identified in sera of injected mice, but with levels that were clearly dependent on the specific chitosan used. We found high DDA low molecular weight chitosans to be efficient protein expressors with minimal or no generation of neutralizing antibodies, while lowering DDA resulted in greater antibody levels and correspondingly lower levels of detected recombinant protein. Histological analyses corroborated these results by revealing greater inflammatory infiltrates in lower DDA chitosans, which produced higher antibody titers. We found, in general, a more efficient delivery of the plasmids by subcutaneous than by intramuscular injection. Specific chitosan carriers were identified to be either efficient non-toxic therapeutic protein delivery systems or vectors for DNA vaccines.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 92%

Chitosan–plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies

et al. 2009

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“…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.…”

Section: Introductionmentioning

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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“…Previous studies have shown that chitosan polyplexes exhibit low cytotoxicity [12][13][14][15] and are suitable for gene delivery to mucosal tissues such as the intestine and the lung in vivo. 12,[16][17][18][19][20][21] In most of these studies, commercially available chitosans of high molecular weights (100-400 kDa) were used. These chitosans form extremely stable polyplexes with DNA, which delays the release of the pDNA, and the physical shape of the polyplexes is dominated by aggregates.…”

Section: Introductionmentioning

confidence: 99%

Improved chitosan-mediated gene delivery based on easily dissociated chitosan polyplexes of highly defined chitosan oligomers

et al. 2004

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Nasal delivery of chitosan–DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice

Cited by 121 publications

References 39 publications

Chitosan–plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies

Chitosan–plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

Improved chitosan-mediated gene delivery based on easily dissociated chitosan polyplexes of highly defined chitosan oligomers

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