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      A Naturally Occurring Hypoallergenic Variant of Vespid Antigen 5 from Polybia scutellaris Venom as a Candidate for Allergen-Specific Immunotherapy

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          Abstract

          Stings by insects from the Hymenoptera order are known to cause life-threatening allergic reactions and impair life quality. Despite the effectiveness of conventional vespid venom immunotherapy, more standardized and safer allergy vaccines are required and recombinant hypoallergenic variants are important clinical tools. Antigen 5 is a major allergen of vespid venoms and it was previously reported that Antigen 5 from Polybia scutellaris (Poly s 5) could be a hypoallergenic variant. In this work we assess the immunological behavior and allergenic activity of Poly s 5 in order to explore its suitability for specific immunotherapy. With this aim, recombinant Poly s 5 was expressed in Pichia pastoris and the presence of cross-reactive epitopes with Pol a 5, a known allergenic Antigen 5, was investigated both at the IgG and IgE levels, by ELISA assays and a basophil-mediator release assay respectively. A molecular model was also built to better understand the relationship between immunological and structural aspects. In mice, Poly s 5 induced IgG antibodies which cross-reacted with Pol a 5. However, Poly s 5 induced only minimal amounts of IgE and was a poor inducer of basophil-mediator release, even when the cells were sensitized with Pol a 5-specific IgE. Moreover, Poly s 5-specific serum showed a specific protective activity and was able to inhibit the Pol a 5-induced basophil degranulation. Structural analysis from the molecular model revealed that a few amino acid substitutions in the N-terminal region of Poly s 5 should lead to an alteration of the surface topography and electrostatic potential of the epitopes which could be responsible for its hypoallergenic behavior. These findings, taken as a whole, show that Poly s 5 is likely a naturally occurring hypoallergenic Antigen 5 variant.

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          Most cited references 31

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            Immunological mechanisms of allergen-specific immunotherapy.

            Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.
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              A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson-Boltzmann equation

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                23 July 2012
                : 7
                : 7
                Affiliations
                [1 ]Departamento de Química Biológica e Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
                [2 ]Departamento de Físico-Matemática, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
                Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg
                Author notes

                Conceived and designed the experiments: SEV MBdJB. Performed the experiments: SEV. Analyzed the data: SEV CMB MBdJB. Contributed reagents/materials/analysis tools: ER CMB. Wrote the paper: SEV MBdJB. Discussed the paper: SEV CMB ER MBdJB.

                [¤]

                Current address: Research Program Infection and Cancer, Division of Viral Transformation Mechanisms, German Cancer Research Centre, Heidelberg, Germany.

                Article
                PONE-D-12-10966
                10.1371/journal.pone.0041351
                3402526
                22844463
                Vinzón et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Biochemistry
                Proteins
                Recombinant Proteins
                Computational Biology
                Macromolecular Structure Analysis
                Protein Structure
                Immunology
                Immunity
                Immunotherapy
                Allergy and Hypersensitivity
                Immune Response
                Medicine
                Clinical Immunology
                Immunity
                Vaccination
                Vaccines
                Vaccine Development
                Drugs and Devices
                Drug Research and Development

                Uncategorized

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