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      Past, present, and future of allergen immunotherapy vaccines

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          Abstract

          Allergen‐specific immunotherapy (AIT) is an allergen‐specific form of treatment for patients suffering from immunoglobulin E (IgE)‐associated allergy; the most common and important immunologically mediated hypersensitivity disease. AIT is based on the administration of the disease‐causing allergen with the goal to induce a protective immunity consisting of allergen‐specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact. Major advantages of AIT over all other existing treatments for allergy are that AIT induces a long‐lasting protection and prevents the progression of disease to severe manifestations. AIT is cost effective because it uses the patient´s own immune system for protection and potentially can be used as a preventive treatment. However, broad application of AIT is limited by mainly technical issues such as the quality of allergen preparations and the risk of inducing side effects which results in extremely cumbersome treatment schedules reducing patient´s compliance. In this article we review progress in AIT made from its beginning and provide an overview of the state of the art, the needs for further development, and possible technical solutions available through molecular allergology. Finally, we consider visions for AIT development towards prophylactic application.

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          Most cited references189

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          Regulatory B cells: origin, phenotype, and function.

          Regulatory B (Breg) cells are immunosuppressive cells that support immunological tolerance. Through the production of interleukin-10 (IL-10), IL-35, and transforming growth factor β (TGF-β), Breg cells suppress immunopathology by prohibiting the expansion of pathogenic T cells and other pro-inflammatory lymphocytes. Recent work has shown that different inflammatory environments induce distinct Breg cell populations. Although these findings highlight the relevance of inflammatory signals in the differentiation of Breg cells, they also raise other questions about Breg cell biology and phenotype. For example, what are the functional properties and phenotype of Breg cells? Can a Breg cell arise at every stage in B cell development? Is inflammation the primary requisite for Breg cell differentiation? Here, we use these questions to discuss the advances in understanding Breg cell biology, with a particular emphasis on their ontogeny; we propose that multiple Breg cell subsets can be induced in response to inflammation at different stages in development.
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            Randomized trial of peanut consumption in infants at risk for peanut allergy.

            The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.
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              Long-term clinical efficacy of grass-pollen immunotherapy.

              Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment. We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease. Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy; P=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863). Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression. Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.
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                Author and article information

                Contributors
                Rudolf.valenta@meduniwien.ac.at
                Journal
                Allergy
                Allergy
                10.1111/(ISSN)1398-9995
                ALL
                Allergy
                John Wiley and Sons Inc. (Hoboken )
                0105-4538
                1398-9995
                29 April 2020
                January 2021
                : 76
                : 1 ( doiID: 10.1111/all.v76.1 )
                : 131-149
                Affiliations
                [ 1 ] Division of Immunopathology Department of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
                [ 2 ] National Research Center, Institute of immunology, FMBA of Russia Moscow Russian Federation
                [ 3 ] Department of Clinical Immunology and Allergy Laboratory of Immunopathology Sechenov First Moscow State Medical University Moscow Russian Federation
                [ 4 ] Department of Immunology and Allergy Russian People’s Friendship University Moscow Russian Federation
                [ 5 ] Institute of Immunology Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
                [ 6 ] Section of Transplantation Immunology Department of Surgery Medical University of Vienna Vienna Austria
                Author notes
                [*] [* ] Correspondence

                Rudolf Valenta, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel, A‐1090 Vienna, Austria

                Email: Rudolf.valenta@ 123456meduniwien.ac.at

                Author information
                https://orcid.org/0000-0001-5304-2042
                https://orcid.org/0000-0001-5343-4230
                https://orcid.org/0000-0002-5825-2687
                https://orcid.org/0000-0003-3433-5071
                https://orcid.org/0000-0003-4768-8693
                https://orcid.org/0000-0003-0430-4952
                https://orcid.org/0000-0001-5944-3365
                Article
                ALL14300
                10.1111/all.14300
                7818275
                32249442
                574b54d8-9dee-4969-b28b-24693e550f82
                © 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 February 2020
                : 25 February 2020
                : 15 March 2020
                Page count
                Figures: 3, Tables: 2, Pages: 19, Words: 15731
                Funding
                Funded by: Megagrant of the Government of the Russian Federation
                Award ID: 14.W03.31.0024
                Funded by: The Russian University Program
                Award ID: 5-100
                Funded by: Austrian Science Fund , open-funder-registry 10.13039/501100002428;
                Award ID: F4605
                Award ID: F4607
                Award ID: F4609
                Award ID: P29991
                Categories
                Review Article
                Reviews
                Custom metadata
                2.0
                January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:21.01.2021

                Immunology
                allergen,allergen‐specific immunotherapy,allergy,molecular allergy vaccines
                Immunology
                allergen, allergen‐specific immunotherapy, allergy, molecular allergy vaccines

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