Antigen-Independent Suppression of the Allergic Immune Response to Bee Venom Phospholipase A2 by DNA Vaccination in CBA/J Mice

Jilek, Samantha; Barbey, Catherine; Spertini, François; Corthésy, Blaise

doi:10.4049/jimmunol.166.5.3612

Cited by 52 publications

(61 citation statements)

References 62 publications

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“…In contrast, after subsequent aerosol challenge the IgE Ab titers were not significantly different from those of untreated control mice, although profound effects on eosinophil infiltration in the airways and local cytokine production were observed. By preventive DNA immunization with naked plasmid DNA IgE Ab production was inhibited in a number of studies, 7,8,[12][13][14][15][16] whereas effective therapeutic treatment of pre-existing IgE Ab responses with plasmid DNA was achieved by three groups only. 7,14,15 The reason for successful inhibition of pre-existing IgE responses may have been that Raz et al 7 used a relatively weak immunization protocol for priming, while Maecker et al 14 vaccinated with an allergen-IL-18 fusion DNA construct to enhance the efficiency of vaccination.…”

Section: Figure 6 Production Of ␤Gal-specific Antibodies After Therapmentioning

confidence: 99%

“…In different animal models, allergen genes have been transferred into the host using various routes, eg as 'naked' plasmid DNA by intramuscular or intradermal injection [7][8][9][10][11][12][13][14][15] or by ballistic transfection with the gene gun, 12,16 as plasmid DNA-polymer complexes by oral delivery, 17 or by means of recombinant mycobacteria as gene vector. 18 Prophylactic DNA immunization lead to inhibition of IgE Ab production 7,8,[12][13][14][15][16] and anaphylactic hypersensitivity, 13,16 as well as decreased airway hyperresponsiveness. 8,14 Induction of CD8 + T cells, as well as a shift towards a Th1 immune response contributed to this effect.…”

Section: Introductionmentioning

confidence: 99%

“…8,14 Induction of CD8 + T cells, as well as a shift towards a Th1 immune response contributed to this effect. 7,8,13,14,19,20 However, successful curative allergen gene transfer for the suppression of already established IgE Ab immune responses was reported only by three groups, 7,14,15 rendering it likely to improve therapeutic DNA vaccination by gene transfer with more efficient vehicles.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

et al. 2002

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DNA-based immunization represents an attractive alternative approach to the current treatment of allergic diseases by specific immunotherapy with allergen extracts. In this study, we used a replication-deficient adenovirus vector (AdCMV), to examine the in vivo efficacy of preventive and therapeutic genetic immunization in a mouse model of type I allergy. Primary immunization with a recombinant adenovirus expressing the model antigen ␤-galactosidase (AdCMV-␤gal) induced a Th1 immune response (predominance of IgG2a antibodies, high frequency of IFN-␥ producing T cells) and large numbers of cytotoxic T lymphocytes. Prophylactic vaccination with AdCMV-␤gal abol-

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Section: Figure 6 Production Of ␤Gal-specific Antibodies After Therapmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

et al. 2002

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“…One strategy is to replace the currently used aluminium salts, which have Th2-polarizing properties, with novel adjuvants such as Tolllike receptor ligands [6,7] that trigger Th1 responses. Another strategy is to increase safety and tolerability of SIT by injecting the allergen in a form that is not recognised by IgE, such as naked DNA vaccines expressing the allergen [8]. Recombinant DNA technology has also allowed the production of mutated allergens with low IgE-binding capacity [9][10][11][12][13][14], such that higher therapeutic doses can be used [15,16].…”

Section: Introductionmentioning

confidence: 99%

Heat denaturation, a simple method to improve the immunotherapeutic potential of allergens

et al. 2005

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Allergen-specific immunotherapy (SIT) leads to a long-term amelioration of IgE-and Th2-mediated allergic diseases. However, SIT efficiency is low, with years of treatment along with frequent allergic side effects. The goal of this study was to reduce the side effects by destroying IgE-binding epitopes, i.e. by heat-denaturation, while preserving the therapeutic effect. Mice were immunised with bee venom, birch pollen, grass pollen or cat hair allergens, or with ovalbumin. Heat-denatured allergens bound less IgE but enhanced Th1-dependent IgG2a production as measured by ELISA. The strong IgG2a antibody responses also prevented allergic anaphylaxis in mice, as measured by body temperature drop after a challenge with a high allergen dose. We found that optimal heat-denaturation of allergens left a small proportion in the native conformation to sufficiently stimulate B cells, while non-B cell-mediated effects were probably amplified. The enhanced immunogenicity of heat-denatured allergens is likely explained by enhanced antigen presentation to T cells due to the particulate nature of heat-denatured proteins. This enables Th1 skewing of the immune response with strong production of IgG2a in mice. Therefore, heat-denaturation represents probably the simplest way to enhance the efficiency of SIT while reducing its side effects. IntroductionIgE-mediated type I hypersensitivity is characterised by prominent activity of mast cells, eosinophils, T helper type 2 (Th2) cells and cytokine actions. Allergenspecific immunotherapy (SIT) leads to long-term amelioration of allergic symptoms and is therefore recommended as a first-line therapy for allergies [1]. During SIT, gradually increasing allergen doses are subcutaneously administered until a maintenance dose is reached, and then treatment continues for 3-5 years. Such lengthy treatment, requiring 30-80 allergen injections, is very costly [2]. Also, SIT frequently causes adverse events due to the interaction of specific IgE with the injected allergen. These adverse events frequently include a local reaction at the site of allergen injection, but also life-threatening systemic reactions such as asthma and anaphylaxis. This is why the administered allergen doses must be kept relatively low, which unfortunately favours Th2 immune responses in contrast to higher doses [3][4][5].Several strategies have been developed to tackle the problems of SIT, i.e. to reduce its side effects and to enhance its immunogenicity. One strategy is to replace the currently used aluminium salts, which have Th2-polarizing properties, with novel adjuvants such as Tolllike receptor ligands [6,7] that trigger Th1 responses. Another strategy is to increase safety and tolerability of SIT by injecting the allergen in a form that is not recognised by IgE, such as naked DNA vaccines Heat-denaturation is well known to reduce the reactogenicity of allergens with IgE, as cooked foods are usually well or better tolerated by allergic individuals [24][25][26]. In this study, we tested whether this very simple strate...

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“…Approaches of redirecting immunity from a Th2 type to Th1 type have also been demonstrated to result in temporary reduction of allergic reactions [6]. However, both autoimmune disease [7] and pathogen infection [8] induced Th1-biased immune responses were found to reduce the likelihood of allergy disease.…”

Section: Introductionmentioning

confidence: 99%

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

et al. 2008

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Asthma is a chronic inflammatory disorder caused by T-cell-mediated inflammation within airways. No antigen-specific treatment has been available. Using an OVA-induced murine asthma model, we find that co-immunization of an OVA epitope peptide with a DNA vaccine encoding the same epitope is able to prevent this experimental asthma as evidenced in the marked reduction of infiltrations of eosinophils and lymphocytes into the site of the allergen challenge. We demonstrate that the prevention of experimental asthma was directly related to the induction of a population of OVA-specific T-regulatory cells (Treg) exhibiting a CD4 1 CD25 À FoxP3 1 phenotype and expressing IL-10, TGF-b and IFN-c following the co-immunization. Blockade of IL-10 and TGF-b of the Treg by anti-IL-10 and TGF-b antibodies is partially able to reverse the suppression in vitro and in vivo, which caused the recurrence of the inflammation. Furthermore, adoptive transfer of the induced Treg is also able to suppress the OVA-induced asthma. To our knowledge, the combination of peptide with its cognate DNA vaccine protect experimental asthma via the induced epitope-specific Treg has not been previously reported and such strategy may lead to a novel immunotherapy against asthma in humans.Key words: Asthma Á Immune regulation Á Tolerance Á Treg cell Á Vaccination IntroductionAsthma is a chronic inflammatory disorder of the airways characterized by airway obstruction, increased airway responsiveness to a variety of stimuli as well as the infiltration by many inflammatory cells, including eosinophils, macrophages, lymphocytes and mast cells into lung tissue. CD4 1 T cells and Th2-biased cytokines (i.e. IL-4, IL-5 and IL-13) are believed to play a central role in the initiation and maintenance of the asthmatic response by regulating the production of IgE and the differentiation, recruitment and activation of mast cells and eosinophils [1][2][3].It has been proposed that Th1 cells, which secrete interferon-g (IFN-g), could protect against allergic disease by inhibiting the proliferation and development of Th2 cells [4] and IgE production [5]. Approaches of redirecting immunity from a Th2 type to Th1 type have also been demonstrated to result in temporary reduction of allergic reactions [6]. However, both autoimmune disease [7] and pathogen infection [8] induced Th1-biased immune responses were found to reduce the likelihood of allergy disease. Hansen et al. demonstrated that antigen-specific Th1 cells were ineffective in reducing the airway hyper-reactivity induced by Th2 cells but caused serious airway inflammation [9]. Thus, immunotherapeutic approaches using Th1 cell responses against asthma are rather complicated.Besides redirecting immunity-based approaches, several other strategies have also been considered to reduce allergic responses, including non-specific immunosuppressive drugs or monoclonal [21,22]. In this report, we further demonstrated that co-immunization of DNA and peptide vaccines against the same epitope-sequence of ovalbumin (OVA, aa 323...

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Antigen-Independent Suppression of the Allergic Immune Response to Bee Venom Phospholipase A2 by DNA Vaccination in CBA/J Mice

Cited by 52 publications

References 62 publications

Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

Heat denaturation, a simple method to improve the immunotherapeutic potential of allergens

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

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