| Immunization with a low-dose replicon DNA vaccine encoding Phl p 5 effectively prevents allergic sensitization. | |
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MedLine Citation:
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PMID: 16950295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Replicase-based DNA vaccines stimulate T(H)1-biased immune responses at ultralow doses and induce self-removal of transfected cells through apoptosis. Both aspects are important requirements for efficient and safe DNA-based immunotherapy of type I allergies. OBJECTIVE: A Sindbis virus replicon-based DNA vaccine encoding the major timothy grass pollen allergen Phl p 5 was evaluated for its antiallergic potential compared with a conventional DNA vaccine in a BALB/c mouse model of allergy. METHODS: Mice were intradermally prevaccinated with plasmid DNA, followed by sensitization and intranasal allergen provocation with recombinant Phl p 5. In vitro proliferation and cytokine secretion was measured in splenocyte cultures. Distribution of IgG1, IgG2a, and IgE antibody subclasses was determined by means of ELISA. IgE-mediated degranulation was measured with the basophil release assay. Bronchoalveolar lavage fluid was analyzed for eosinophils, IL-4, IL-5, IL-13, and IFN-gamma. Mucus production, inflammatory infiltrates, and epithelial damage were determined in lung sections. RESULTS: Both vaccines induced T(H)1-biased immune responses, resulting in suppression of functional IgE, reduction of eosinophilia in bronchoalveolar lavage fluid, and alleviation of lung pathology. However, immunization with the replicon DNA vaccine elicited these effects at a 100-fold lower dose compared with the conventional DNA vaccine. CONCLUSIONS: The increased immunogenicity of replicon-based DNA vaccines allows for application of extremely low doses, thereby eliminating the concerns associated with conventional DNA vaccines, which have to be administered at milligram amounts to induce immune reactions in human subjects. CLINICAL IMPLICATIONS: Their high safety profile makes replicon-based DNA vaccines promising candidates for treatment of type I allergies in the clinic. |
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Authors:
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Maximilian Gabler; Sandra Scheiblhofer; Kerstin Kern; Wolfgang W Leitner; Angelika Stoecklinger; Cornelia Hauser-Kronberger; Beate Alinger; Berta Lechner; Monika Prinz; Susanne Vrtala; Rudolf Valenta; Josef Thalhamer; Richard Weiss |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-06-06 |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 118 ISSN: 0091-6749 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-04 Completed Date: 2006-10-17 Revised Date: 2011-04-06 |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 734-41 Citation Subset: AIM; IM |
Affiliation:
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Christian Doppler Laboratory for Allergy Diagnostic and Therapy, Department of Molecular Biology, University of Salzburg, Austria. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Cells, Cultured Dose-Response Relationship, Immunologic Female Injections, Intradermal Mice Mice, Inbred BALB C Plant Proteins / administration & dosage, genetics*, immunology* RNA Replicase / genetics, immunology Replicon / immunology* Respiratory Hypersensitivity / immunology*, prevention & control* Sindbis Virus / enzymology, genetics, immunology Th1 Cells / immunology Vaccines, DNA / administration & dosage, immunology* Viral Vaccines / administration & dosage, genetics, immunology |
| Grant Support | |
ID/Acronym/Agency:
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L 181-B13//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/Phl p V protein, Phleum pratense; 0/Plant Proteins; 0/Vaccines, DNA; 0/Viral Vaccines; EC 2.7.7.48/RNA Replicase |
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