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      Preventive Allergen-Specific Vaccination Against Allergy: Mission Possible?

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          Abstract

          Vaccines for infectious diseases have improved the life of the human species in a tremendous manner. The principle of vaccination is to establish de novo adaptive immune response consisting of antibody and T cell responses against pathogens which should defend the vaccinated person against future challenge with the culprit pathogen. The situation is completely different for immunoglobulin E (IgE)-associated allergy, an immunologically-mediated hypersensitivity which is already characterized by increased IgE antibody levels and T cell responses against per se innocuous antigens (i.e., allergens). Thus, allergic patients suffer from a deviated hyper-immunity against allergens leading to inflammation upon allergen contact. Paradoxically, vaccination with allergens, termed allergen-specific immunotherapy (AIT), induces a counter immune response based on the production of high levels of allergen-specific IgG antibodies and alterations of the adaptive cellular response, which reduce allergen-induced symptoms of allergic inflammation. AIT was even shown to prevent the progression of mild to severe forms of allergy. Consequently, AIT can be considered as a form of therapeutic vaccination. In this article we describe a strategy and possible road map for the use of an AIT approach for prophylactic vaccination against allergy which is based on new molecular allergy vaccines. This road map includes the use of AIT for secondary preventive vaccination to stop the progression of clinically silent allergic sensitization toward symptomatic allergy and ultimately the prevention of allergic sensitization by maternal vaccination and/or early primary preventive vaccination of children. Prophylactic allergy vaccination with molecular allergy vaccines may allow halting the allergy epidemics affecting almost 30% of the population as it has been achieved for vaccination against infectious diseases.

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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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            Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers

            Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells. Suppression of TH2 immunity can occur as a consequence of either deletion or anergy of antigen-specific T cells; induction of antigen-specific regulatory T cells; or immune deviation in favor of TH1 responses. It is not clear whether the altered long-term memory resides within the T-cell or the B-cell compartment. Recent data highlight the role of IL-10-producing regulatory B cells and "protective" antibodies that likely contribute to long-term tolerance. Understanding mechanisms underlying induction and persistence of tolerance should identify predictive biomarkers of clinical response and discover novel and more effective strategies for immunotherapy.
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              Vaccines for the twenty-first century society

              The childhood vaccination campaigns of the twentieth century represent one of the great success stories of modern medicine. But are we yet to realize the full potential of vaccines? This article discusses the medical needs of the twenty-first century society and proposes that new vaccines will play a major part in addressing these needs.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                07 July 2020
                2020
                : 11
                : 1368
                Affiliations
                [1] 1Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna , Vienna, Austria
                [2] 2Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University , Moscow, Russia
                [3] 3Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna , Vienna, Austria
                [4] 4Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden
                [5] 5NRC Institute of Immunology FMBA of Russia , Moscow, Russia
                [6] 6Karl Landsteiner University of Health Sciences , Krems an der Donau, Austria
                Author notes

                Edited by: Fabio Bagnoli, GlaxoSmithKline, Italy

                Reviewed by: Andreas L. Lopata, James Cook University, Australia; Yvonne Paterson, University of Pennsylvania, United States

                *Correspondence: Winfried F. Pickl winfried.pickl@ 123456meduniwien.ac.at

                This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.01368
                7358538
                32733455
                e5e8f899-657f-40b3-8cbe-d92bbdc5469f
                Copyright © 2020 Tulaeva, Kratzer, Campana, Curin, van Hage, Karsonova, Riabova, Karaulov, Khaitov, Pickl and Valenta.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 February 2020
                : 28 May 2020
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 110, Pages: 17, Words: 12342
                Funding
                Funded by: Austrian Science Fund 10.13039/501100002428
                Categories
                Immunology
                Review

                Immunology
                vaccine,vaccination,allergy,allergen,allergen-specific immunotherapy,therapeutic vaccine,molecular allergy vaccine,ige

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