Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice

Chew, Joon Lin; Wolfowicz, Claudia B.; Mao, Hai‐Quan; Leong, Kam W.; Chua, Kaw Yan

doi:10.1016/s0264-410x(03)00228-7

Cited by 104 publications

(60 citation statements)

References 42 publications

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“…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. Other in vivo studies report appreciable protein expression using chitosan as condensing carrier for plasmid delivery.…”

Section: Introductionmentioning

confidence: 99%

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: 99%

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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“…In Th1 disease models such as experimental autoimmune encephalomyelitis or diabetes, treatment via oral tolerance induction is associated with a shift toward a Th2 immune response (12,20). In contrast, in allergy models, which are characterized by a Th2 cytokine profile, tolerance induction led to a suppression of the Th2 response (21,30,36), which was also observed by Roy et al and Chew et al using allergen-encoding chitosan-DNA NP (13,35).…”

Section: Figmentioning

confidence: 58%

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

Goldmann

Ensminger

Spriewald

2012

Clin. Vaccine Immunol.

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Oral tolerance is a promising approach to induce unresponsiveness to various antigens. The development of tolerogenic vaccines could be exploited in modulating the immune response in autoimmune disease and allograft rejection. In this study, we investigated a nonviral gene transfer strategy for inducing oral tolerance via antigen-encoding chitosan-DNA nanoparticles (NP). Oral application of ovalbumin (OVA)-encoding chitosan-DNA NP (OVA-NP) suppressed the OVA-specific delayed-type hypersensitivity (DTH) response and anti-OVA antibody formation, as well as spleen cell proliferation following OVA stimulation. Cytokine expression patterns following OVA stimulation in vitro showed a shift from a Th1 toward a Th2/Th3 response. The OVA-NP-induced tolerance was transferable from donor to naïve recipient mice via adoptive spleen cell transfer and was mediated by CD4 ؉ CD25 ؉ T cells. These findings indicate that nonviral oral gene transfer can induce regulatory T cells for antigen-specific immune modulation.

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“…Mucoadhesive chitosan microparticles represent a promising formulation for use in sublingual allergy vaccines. In other studies, chitosan nanoparticles, containing plasmid DNA encoding the HDM allergen Dermatophagoides pteronyssinus 2 (Der p2) 100 or Der p1, 101 induced IFN-c in serum and prevented subsequent sensitization of Th2 cell-regulated allergen-specific IgE responses following oral vaccination in mice. The data on Der p2 also indicate that oral administration of chitosan-Der p2 DNA nanoparticles results in the expression of Der p2 by epithelial cells in both the stomach and small intestine.…”

Section: Ctb-agmentioning

confidence: 98%

“…95 Der f-CS nanovaccine/i.n. ; 98 chitosan-pDer p2 100 or pDer p1 nanoparticles/oral 101 Mucoadhesive chitosan-formulated OVA/sublingual 99 Antigen-probiotics Co-administration/oral 102 and i.n. 104 Recombinant Der p1 111-139 105 and Bet v 1 107 producing probiotics/i.n.…”

Section: Combination Effect Animal Modelmentioning

confidence: 99%

Strategies of mucosal immunotherapy for allergic diseases

Chuang

Chiang

2011

Cell Mol Immunol

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Incidences of allergic disease have recently increased worldwide. Allergen-specific immunotherapy (SIT) has long been a controversial treatment for allergic diseases. Although beneficial effects on clinically relevant outcomes have been demonstrated in clinical trials by subcutaneous immunotherapy (SCIT), there remains a risk of severe and sometimes fatal anaphylaxis. Mucosal immunotherapy is one advantageous choice because of its non-injection routes of administration and lower side-effect profile. This study reviews recent progress in mucosal immunotherapy for allergic diseases. Administration routes, antigen quality and quantity, and adjuvants used are major considerations in this field. Also, direct uses of unique probiotics, or specific cytokines, have been discussed. Furthermore, some researchers have reported new therapeutic ideas that combine two or more strategies. The most important strategy for development of mucosal therapies for allergic diseases is the improvement of antigen formulation, which includes continuous searching for efficient adjuvants, collecting more information about dominant T-cell epitopes of allergens, and having the proper combination of each. In clinics, when compared to other mucosal routes, sublingual immunotherapy (SLIT) is a preferred choice for therapeutic administration, although local and systemic side effects have been reported. Additionally, not every allergen has the same beneficial effect. Further studies are needed to determine the benefits of mucosal immunotherapy for different allergic diseases after comparison of the different administration routes in children and adults. Data collected from large, well-designed, double-blind, placebo-controlled, and randomized trials, with post-treatment follow-up, can provide robust substantiation of current evidence.

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Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice

Cited by 104 publications

References 42 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

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

Strategies of mucosal immunotherapy for allergic diseases

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