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      All the small things: How virus‐like particles and liposomes modulate allergic immune responses

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          Abstract

          Recent years have seen a dramatic increase in the range of applications of virus‐like nanoparticle (VNP)‐ and liposome‐based antigen delivery systems for the treatment of allergies. These platforms rely on a growing number of inert virus‐backbones or distinct lipid formulations and intend to engage the host's innate and/or adaptive immune system by virtue of their co‐delivered immunogens. Due to their particulate nature, VNP and liposomal preparations are also capable of breaking tolerance against endogenous cytokines, Igs, and their receptors, allowing for the facile induction of anti‐cytokine, anti‐IgE, or anti‐FcεR antibodies in the host. We here discuss the “pros and cons” of inducing such neutralizing autoantibodies. Moreover, we cover another major theme of the last years, i.e., the engineering of non‐anaphylactogenic particles and the elucidation of the parameters relevant for the specific trafficking and processing of such particles in vivo. Finally, we put the various technical advances in VNP‐ and liposome‐research into (pre‐)clinical context by referring and critically discussing the relevant studies performed to treat allergic diseases.

          Abstract

          Virus‐like nanoparticles (VNP) and liposomes are innovative therapeutic platforms for the modulation of allergic immune responses. They variably deliver cues for innate‐, antigen‐, and cytokine‐receptors and thereby induce blocking antibodies (either against effector cytokines of allergens) and/or T cell tolerance.

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          Most cited references141

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          Liposomes as nanomedical devices

          Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials.
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            Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial

            Eosinophilia is associated with worsening asthma severity and decreased lung function, with increased exacerbation frequency. We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor α that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.
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              Lebrikizumab treatment in adults with asthma.

              Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity. We conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level. At baseline, patients had a mean FEV(1) that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV(1) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV(1) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV(1) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P = 0.045). Lebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163 .).
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                Author and article information

                Contributors
                winfried.pickl@meduniwien.ac.at
                Journal
                Eur J Immunol
                Eur. J. Immunol
                10.1002/(ISSN)1521-4141
                EJI
                European Journal of Immunology
                John Wiley and Sons Inc. (Hoboken )
                0014-2980
                1521-4141
                15 December 2019
                January 2020
                : 50
                : 1 ( doiID: 10.1002/eji.v50.1 )
                : 17-32
                Affiliations
                [ 1 ] Institute of Immunology Center for Pathophysiology Infectiology and Immunology Medical University of Vienna Austria
                Author notes
                [*] [* ] Full correspondence Winfried F. Pickl, MD, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria

                Email: winfried.pickl@ 123456meduniwien.ac.at

                Author information
                https://orcid.org/0000-0003-1091-4327
                https://orcid.org/0000-0003-0430-4952
                Article
                EJI4672
                10.1002/eji.201847810
                6973265
                31799700
                85853c25-f4c9-48af-9b95-8ccd8bc35927
                © 2019 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

                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
                : 29 July 2019
                : 15 October 2019
                : 02 December 2019
                Page count
                Figures: 3, Tables: 3, Pages: 16, Words: 13165
                Funding
                Funded by: Austrian Science Foundation
                Funded by: Austrian Science Fund , open-funder-registry 10.13039/501100002428;
                Award ID: DK‐W1248
                Award ID: Pickl
                Award ID: Winfried
                Award ID: SFB F4609
                Categories
                Review|Clinical
                Highlights
                Reviews
                Clinical
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:21.01.2020

                Immunology
                allergy,immunotherapy,neutralizing antibodies,liposomes,virus‐like particles
                Immunology
                allergy, immunotherapy, neutralizing antibodies, liposomes, virus‐like particles

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