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Kappen JH, Agache I, Jutel M, Pillai P, Corrigan CJ. Allergen Immunotherapy for Asthma. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:23-30. [PMID: 38013158 DOI: 10.1016/j.jaip.2023.11.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/06/2023] [Accepted: 11/06/2023] [Indexed: 11/29/2023]
Abstract
Allergen immunotherapy is a disease-modifying treatment for IgE-mediated allergies reducing disease burden and symptoms in patients with allergic rhinitis, with or without asthma. The growing evidence that allergen immunotherapy also has the potential to facilitate achieving asthma control in patients with allergic asthma resulted in its acknowledgment by international bodies (Global Initiative for Asthma and European Academy of Allergy and Clinical Immunology) as add-on treatment for mild/moderate asthma. Although there have been promising developments in biomarkers for patient selection and for allergen immunotherapy efficacy evaluation in patients with asthma, a lot more data are still required.
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Affiliation(s)
- Jasper H Kappen
- Department of Pulmonology, STZ Centre of Excellence for Asthma, COPD and Respiratory Allergy, Franciscus & Vlietland, Rotterdam, The Netherlands; Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
| | | | - Marek Jutel
- Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland; ALL-MED Medical Research Institute, Wroclaw, Poland
| | - Prathap Pillai
- Department of Adult Allergy, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; King's Centre for Lung Health, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Chris J Corrigan
- King's Centre for Lung Health, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
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Utembe W, Andraos C, Gulumian M. Immunotoxicity of engineered nanomaterials and their role in asthma. Crit Rev Toxicol 2023; 53:491-505. [PMID: 37933836 DOI: 10.1080/10408444.2023.2270519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 10/03/2023] [Indexed: 11/08/2023]
Abstract
The toxicity of engineered nanomaterials (ENMs) in vivo and in vitro has formed the basis of most studies. However, the toxicity of ENMs, particularly on the immune system, i.e. immunotoxicity, and their role in manipulating it, are less known. This review addresses the initiation or exacerbation as well as the attenuation of allergic asthma by a variety of ENMs and how they may be used in drug delivery to enhance the treatment of asthma. This review also highlights a few research gaps in the study of the immunotoxicity of ENMs, for example, the potential drawbacks of assays used in immunotoxicity assays; the potential role of hormesis during dosing of ENMs; and the variables that result in discrepancies among different studies, such as the physicochemical properties of ENMs, differences in asthmatic animal models, and different routes of administration.
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Affiliation(s)
- Wells Utembe
- Toxicology and Biochemistry, National Institute for Occupational Health, National Health Laboratory Service, Johannesburg, South Africa
- Department of Environmental Health, University of Johannesburg, Johannesburg, South Africa
- Environmental Health Division, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Charlene Andraos
- Toxicology and Biochemistry, National Institute for Occupational Health, National Health Laboratory Service, Johannesburg, South Africa
- Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mary Gulumian
- Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa
- Haematology and Molecular Medicine Department, University of the Witwatersrand, Johannesburg, South Africa
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Reginald K, Chew FT. Current practices and future trends in cockroach allergen immunotherapy. Mol Immunol 2023; 161:11-24. [PMID: 37480600 DOI: 10.1016/j.molimm.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 07/02/2023] [Accepted: 07/05/2023] [Indexed: 07/24/2023]
Abstract
PURPOSE OF REVIEW This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects. SUMMARY Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response.
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Affiliation(s)
- Kavita Reginald
- Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Selangor, Malaysia.
| | - Fook Tim Chew
- Department of Biological Sciences, Faculty of Science, National University of Singapore, 117543, Singapore
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Šošić L, Paolucci M, Flory S, Jebbawi F, Kündig TM, Johansen P. Allergen immunotherapy: progress and future outlook. Expert Rev Clin Immunol 2023:1-25. [PMID: 37122076 DOI: 10.1080/1744666x.2023.2209319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
INTRODUCTION Allergy, the immunological hypersensitivity to innocuous environmental compounds, is a global health problem. The disease triggers, allergens, are mostly proteins contained in various natural sources such as plant pollen, animal dander, dust mites, foods, fungi and insect venoms. Allergies can manifest with a wide range of symptoms in various organs, and be anything from just tedious to life-threatening. A majority of all allergy patients are self-treated with symptom-relieving medicines, while allergen immunotherapy (AIT) is the only causative treatment option. AREAS COVERED This review will aim to give an overview of the state-of-the-art allergy management, including the use of new biologics and the application of biomarkers, and a special emphasis and discussion on current research trends in the field of AIT. EXPERT OPINION Conventional AIT has proven effective, but the years-long treatment compromises patient compliance. Moreover, AIT is typically not offered in food allergy. Hence, there is a need for new, effective and safe AIT methods. Novel routes of administration (e.g. oral and intralymphatic), hypoallergenic AIT products and more effective adjuvants holds great promise. Most recently, the development of allergen-specific monoclonal antibodies for passive immunotherapy may also allow treatment of patients currently not treated or treatable.
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Affiliation(s)
- Lara Šošić
- Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
| | - Marta Paolucci
- Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
| | - Stephan Flory
- Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
| | - Fadi Jebbawi
- Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
| | - Thomas M Kündig
- Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
- Department of Dermatology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
| | - Pål Johansen
- Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
- Department of Dermatology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
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Fiala S, Fleit HB. Clinical and experimental treatment of allergic asthma with an emphasis on allergen immunotherapy and its mechanisms. Clin Exp Immunol 2023; 212:14-28. [PMID: 36879430 PMCID: PMC10081111 DOI: 10.1093/cei/uxad031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 01/23/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Allergen immunotherapy (AIT) is currently the only form of treatment that modifies allergic asthma. Pharmacotherapy alone seeks to control the symptoms of allergic asthma, allergic rhinitis, and other atopic conditions. In contrast, AIT can induce long-term physiological modifications through the immune system. AIT enables individuals to live improved lives many years after treatment ends, where they are desensitized to the allergen(s) used or no longer have significant allergic reactions upon allergen provocation. The leading forms of treatment with AIT involve injections of allergen extracts with increasing doses via the subcutaneous route or drops/tablets via the sublingual route for several years. Since the initial attempts at this treatment as early as 1911 by Leonard Noon, the mechanisms by which AIT operates remain unclear. This literature-based review provides the primary care practitioner with a current understanding of the mechanisms of AIT, including its treatment safety, protocols, and long-term efficacy. The primary mechanisms underlying AIT include changes in immunoglobulin classes (IgA, IgE, and IgG), immunosuppressive regulatory T-cell induction, helper T cell type 2 to helper T cell type 1 cell/cytokine profile shifts, decreased early-phase reaction activity and mediators, and increased production of IL-10, IL-35, TGF-β, and IFN-γ. Using the databases PubMed and Embase, a selective literature search was conducted searching for English, full-text, reviews published between 2015 and 2022 using the keywords (with wildcards) "allerg*," "immunotherap*," "mechanis*," and "asthma." Among the cited references, additional references were identified using a manual search.
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Affiliation(s)
- Scott Fiala
- Department of Pathology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
| | - Howard B Fleit
- Department of Pathology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
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Wise SK, Damask C, Roland LT, Ebert C, Levy JM, Lin S, Luong A, Rodriguez K, Sedaghat AR, Toskala E, Villwock J, Abdullah B, Akdis C, Alt JA, Ansotegui IJ, Azar A, Baroody F, Benninger MS, Bernstein J, Brook C, Campbell R, Casale T, Chaaban MR, Chew FT, Chambliss J, Cianferoni A, Custovic A, Davis EM, DelGaudio JM, Ellis AK, Flanagan C, Fokkens WJ, Franzese C, Greenhawt M, Gill A, Halderman A, Hohlfeld JM, Incorvaia C, Joe SA, Joshi S, Kuruvilla ME, Kim J, Klein AM, Krouse HJ, Kuan EC, Lang D, Larenas-Linnemann D, Laury AM, Lechner M, Lee SE, Lee VS, Loftus P, Marcus S, Marzouk H, Mattos J, McCoul E, Melen E, Mims JW, Mullol J, Nayak JV, Oppenheimer J, Orlandi RR, Phillips K, Platt M, Ramanathan M, Raymond M, Rhee CS, Reitsma S, Ryan M, Sastre J, Schlosser RJ, Schuman TA, Shaker MS, Sheikh A, Smith KA, Soyka MB, Takashima M, Tang M, Tantilipikorn P, Taw MB, Tversky J, Tyler MA, Veling MC, Wallace D, Wang DY, White A, Zhang L. International consensus statement on allergy and rhinology: Allergic rhinitis - 2023. Int Forum Allergy Rhinol 2023; 13:293-859. [PMID: 36878860 DOI: 10.1002/alr.23090] [Citation(s) in RCA: 142] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/11/2022] [Accepted: 09/13/2022] [Indexed: 03/08/2023]
Abstract
BACKGROUND In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.
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Affiliation(s)
- Sarah K Wise
- Otolaryngology-HNS, Emory University, Atlanta, Georgia, USA
| | - Cecelia Damask
- Otolaryngology-HNS, Private Practice, University of Central Florida, Lake Mary, Florida, USA
| | - Lauren T Roland
- Otolaryngology-HNS, Washington University, St. Louis, Missouri, USA
| | - Charles Ebert
- Otolaryngology-HNS, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Joshua M Levy
- Otolaryngology-HNS, Emory University, Atlanta, Georgia, USA
| | - Sandra Lin
- Otolaryngology-HNS, University of Wisconsin, Madison, Wisconsin, USA
| | - Amber Luong
- Otolaryngology-HNS, McGovern Medical School of the University of Texas, Houston, Texas, USA
| | - Kenneth Rodriguez
- Otolaryngology-HNS, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Ahmad R Sedaghat
- Otolaryngology-HNS, University of Cincinnati, Cincinnati, Ohio, USA
| | - Elina Toskala
- Otolaryngology-HNS, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | | | - Baharudin Abdullah
- Otolaryngology-HNS, Universiti Sains Malaysia, Kubang, Kerian, Kelantan, Malaysia
| | - Cezmi Akdis
- Immunology, Infectious Diseases, Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
| | - Jeremiah A Alt
- Otolaryngology-HNS, University of Utah, Salt Lake City, Utah, USA
| | | | - Antoine Azar
- Allergy/Immunology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Fuad Baroody
- Otolaryngology-HNS, University of Chicago, Chicago, Illinois, USA
| | | | | | - Christopher Brook
- Otolaryngology-HNS, Harvard University, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Raewyn Campbell
- Otolaryngology-HNS, Macquarie University, Sydney, NSW, Australia
| | - Thomas Casale
- Allergy/Immunology, University of South Florida College of Medicine, Tampa, Florida, USA
| | - Mohamad R Chaaban
- Otolaryngology-HNS, Cleveland Clinic, Case Western Reserve University, Cleveland, Ohio, USA
| | - Fook Tim Chew
- Allergy/Immunology, Genetics, National University of Singapore, Singapore, Singapore
| | - Jeffrey Chambliss
- Allergy/Immunology, University of Texas Southwestern, Dallas, Texas, USA
| | - Antonella Cianferoni
- Allergy/Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | | | | | | | - Anne K Ellis
- Allergy/Immunology, Queens University, Kingston, ON, Canada
| | | | - Wytske J Fokkens
- Otorhinolaryngology, Amsterdam University Medical Centres, Amsterdam, Netherlands
| | | | - Matthew Greenhawt
- Allergy/Immunology, Pediatrics, University of Colorado, Children's Hospital Colorado, Aurora, Colorado, USA
| | - Amarbir Gill
- Otolaryngology-HNS, University of Michigan, Ann Arbor, Michigan, USA
| | - Ashleigh Halderman
- Otolaryngology-HNS, University of Texas Southwestern, Dallas, Texas, USA
| | - Jens M Hohlfeld
- Respiratory Medicine, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover Medical School, German Center for Lung Research, Hannover, Germany
| | | | - Stephanie A Joe
- Otolaryngology-HNS, University of Illinois Chicago, Chicago, Illinois, USA
| | - Shyam Joshi
- Allergy/Immunology, Oregon Health and Science University, Portland, Oregon, USA
| | | | - Jean Kim
- Otolaryngology-HNS, Johns Hopkins University, Baltimore, Maryland, USA
| | - Adam M Klein
- Otolaryngology-HNS, Emory University, Atlanta, Georgia, USA
| | - Helene J Krouse
- Otorhinolaryngology Nursing, University of Texas Rio Grande Valley, Edinburg, Texas, USA
| | - Edward C Kuan
- Otolaryngology-HNS, University of California Irvine, Orange, California, USA
| | - David Lang
- Allergy/Immunology, Cleveland Clinic, Cleveland, Ohio, USA
| | | | | | - Matt Lechner
- Otolaryngology-HNS, University College London, Barts Health NHS Trust, London, UK
| | - Stella E Lee
- Otolaryngology-HNS, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Victoria S Lee
- Otolaryngology-HNS, University of Illinois Chicago, Chicago, Illinois, USA
| | - Patricia Loftus
- Otolaryngology-HNS, University of California San Francisco, San Francisco, California, USA
| | - Sonya Marcus
- Otolaryngology-HNS, Stony Brook University, Stony Brook, New York, USA
| | - Haidy Marzouk
- Otolaryngology-HNS, State University of New York Upstate, Syracuse, New York, USA
| | - Jose Mattos
- Otolaryngology-HNS, University of Virginia, Charlottesville, Virginia, USA
| | - Edward McCoul
- Otolaryngology-HNS, Ochsner Clinic, New Orleans, Louisiana, USA
| | - Erik Melen
- Pediatric Allergy, Karolinska Institutet, Stockholm, Sweden
| | - James W Mims
- Otolaryngology-HNS, Wake Forest University, Winston Salem, North Carolina, USA
| | - Joaquim Mullol
- Otorhinolaryngology, Hospital Clinic Barcelona, Barcelona, Spain
| | - Jayakar V Nayak
- Otolaryngology-HNS, Stanford University, Palo Alto, California, USA
| | - John Oppenheimer
- Allergy/Immunology, Rutgers, State University of New Jersey, Newark, New Jersey, USA
| | | | - Katie Phillips
- Otolaryngology-HNS, University of Cincinnati, Cincinnati, Ohio, USA
| | - Michael Platt
- Otolaryngology-HNS, Boston University, Boston, Massachusetts, USA
| | | | | | - Chae-Seo Rhee
- Rhinology/Allergy, Seoul National University Hospital and College of Medicine, Seoul, Korea
| | - Sietze Reitsma
- Otolaryngology-HNS, University of Amsterdam, Amsterdam, Netherlands
| | - Matthew Ryan
- Otolaryngology-HNS, University of Texas Southwestern, Dallas, Texas, USA
| | - Joaquin Sastre
- Allergy, Fundacion Jiminez Diaz, University Autonoma de Madrid, Madrid, Spain
| | - Rodney J Schlosser
- Otolaryngology-HNS, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Theodore A Schuman
- Otolaryngology-HNS, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Marcus S Shaker
- Allergy/Immunology, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Aziz Sheikh
- Primary Care, University of Edinburgh, Edinburgh, Scotland
| | - Kristine A Smith
- Otolaryngology-HNS, University of Utah, Salt Lake City, Utah, USA
| | - Michael B Soyka
- Otolaryngology-HNS, University of Zurich, University Hospital of Zurich, Zurich, Switzerland
| | - Masayoshi Takashima
- Otolaryngology-HNS, Houston Methodist Academic Institute, Houston, Texas, USA
| | - Monica Tang
- Allergy/Immunology, University of California San Francisco, San Francisco, California, USA
| | | | - Malcolm B Taw
- Integrative East-West Medicine, University of California Los Angeles, Westlake Village, California, USA
| | - Jody Tversky
- Allergy/Immunology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Matthew A Tyler
- Otolaryngology-HNS, University of Minnesota, Minneapolis, Minnesota, USA
| | - Maria C Veling
- Otolaryngology-HNS, University of Texas Southwestern, Dallas, Texas, USA
| | - Dana Wallace
- Allergy/Immunology, Nova Southeastern University, Ft. Lauderdale, Florida, USA
| | - De Yun Wang
- Otolaryngology-HNS, National University of Singapore, Singapore, Singapore
| | - Andrew White
- Allergy/Immunology, Scripps Clinic, San Diego, California, USA
| | - Luo Zhang
- Otolaryngology-HNS, Beijing Tongren Hospital, Beijing, China
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Lipid nanoparticles technology in vaccines: Shaping the future of prophylactic medicine. Colloids Surf B Biointerfaces 2023; 222:113111. [PMID: 36586237 DOI: 10.1016/j.colsurfb.2022.113111] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 12/07/2022] [Accepted: 12/18/2022] [Indexed: 12/24/2022]
Abstract
Throughout decades, the intrinsic power of the immune system to fight pathogens has inspired researchers to develop techniques that enable the prevention or treatment of infections via boosting the immune response against the target pathogens, which has led to the evolution of vaccines. The recruitment of Lipid nanoparticles (LNPs) as either vaccine delivery platforms or immunogenic modalities has witnessed a breakthrough recently, which has been crowned with the development of effective LNPs-based vaccines against COVID-19. In the current article, we discuss some principles of such a technology, with a special focus on the technical aspects from a translational perspective. Representative examples of LNPs-based vaccines against cancer, COVID-19, as well as other infectious diseases, autoimmune diseases, and allergies are highlighted, considering the challenges and promises. Lastly, the key features that can improve the clinical translation of this area of endeavor are inspired.
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Zinkhan S, Thoms F, Augusto G, Vogel M, Bachmann MF. On the role of allergen-specific IgG subclasses for blocking human basophil activation. Front Immunol 2022; 13:892631. [PMID: 36275723 PMCID: PMC9582512 DOI: 10.3389/fimmu.2022.892631] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 09/16/2022] [Indexed: 11/30/2022] Open
Abstract
Successful treatment of IgE mediated allergies by allergen-specific immunotherapy (AIT) usually correlates with the induction of allergen-specific IgG4. However, it is not clear whether IgG4 prevents the allergic reaction more efficiently than other IgG subclasses. Here we aimed to compare allergen-specific monoclonal IgG1 and IgG4 antibodies in their capacity to inhibit type I allergic reactions by engaging FcγRIIb. We found that IgG1, which is the dominant subclass induced by viruses, binds with a similar affinity to the FcγRIIb as IgG4 and is comparable at blocking human basophil activation from allergic patients; both by neutralizing the allergen as well as engaging the inhibitory receptor FcγRIIb. Hence, the IgG subclass plays a limited role for the protective efficacy of AIT even if IgG4 is considered the best correlate of protection, most likely simply because it is the dominant subclass induced by classical AITs.
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Affiliation(s)
- Simon Zinkhan
- Department of Immunology, University Clinic of Rheumatology and Immunology, Inselspital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | | | - Gilles Augusto
- Department of Immunology, University Clinic of Rheumatology and Immunology, Inselspital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
- Nuffield Department of Medicine, The Henry Wellcome Building for Molecular Physiology, The Jenner Institute, University of Oxford, Oxford, United Kingdom
| | - Monique Vogel
- Department of Immunology, University Clinic of Rheumatology and Immunology, Inselspital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Martin F. Bachmann
- Department of Immunology, University Clinic of Rheumatology and Immunology, Inselspital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
- Nuffield Department of Medicine, The Henry Wellcome Building for Molecular Physiology, The Jenner Institute, University of Oxford, Oxford, United Kingdom
- *Correspondence: Martin F. Bachmann,
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9
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Li H, Yang YG, Sun T. Nanoparticle-Based Drug Delivery Systems for Induction of Tolerance and Treatment of Autoimmune Diseases. Front Bioeng Biotechnol 2022; 10:889291. [PMID: 35464732 PMCID: PMC9019755 DOI: 10.3389/fbioe.2022.889291] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 03/10/2022] [Indexed: 11/13/2022] Open
Abstract
Autoimmune disease is a chronic inflammatory disease caused by disorders of immune regulation. Antigen-specific immunotherapy has the potential to inhibit the autoreactivity of inflammatory T cells and induce antigen-specific immune suppression without impairing normal immune function, offering an ideal strategy for autoimmune disease treatment. Tolerogenic dendritic cells (Tol DCs) with immunoregulatory functions play important roles in inducing immune tolerance. However, the effective generation of tolerogenic DCs in vivo remains a great challenge. The application of nanoparticle-based drug delivery systems in autoimmune disease treatment can increase the efficiency of inducing antigen-specific tolerance in vivo. In this review, we discuss multiple nanoparticles, with a focus on their potential in treatment of autoimmune diseases. We also discuss how the physical properties of nanoparticles influence their therapeutic efficacy.
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Affiliation(s)
- He Li
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- Department of Rehabilitation Medicine, The First Hospital, Jilin University, Changchun, China
| | - Yong-Guang Yang
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
| | - Tianmeng Sun
- Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, China
- National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
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10
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Allergen Immunotherapy: Current and Future Trends. Cells 2022; 11:cells11020212. [PMID: 35053328 PMCID: PMC8774202 DOI: 10.3390/cells11020212] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 02/06/2023] Open
Abstract
Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.
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de Blay F, Gherasim A, Casale TB, Doyen V, Bernstein D. Which patients with asthma are most likely to benefit from allergen immunotherapy? J Allergy Clin Immunol 2022; 149:833-843. [DOI: 10.1016/j.jaci.2022.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/14/2022] [Accepted: 01/17/2022] [Indexed: 10/19/2022]
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Pashkina E, Evseenko V, Dumchenko N, Zelikman M, Aktanova A, Bykova M, Khvostov M, Dushkin A, Kozlov V. Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy. NANOMATERIALS 2021; 12:nano12010148. [PMID: 35010098 PMCID: PMC8746317 DOI: 10.3390/nano12010148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/29/2021] [Accepted: 12/30/2021] [Indexed: 11/23/2022]
Abstract
The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.
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Affiliation(s)
- Ekaterina Pashkina
- Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya, 6300099 Novosibirsk, Russia; (A.A.); (V.K.)
- Correspondence:
| | - Veronika Evseenko
- Institute of Solid State Chemistry and Mechanochemistry, 18, Kutateladze, 630090 Novosibirsk, Russia; (V.E.); (M.Z.); (A.D.)
| | - Natalya Dumchenko
- State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Novosibirsk Oblast, Russia;
| | - Maxim Zelikman
- Institute of Solid State Chemistry and Mechanochemistry, 18, Kutateladze, 630090 Novosibirsk, Russia; (V.E.); (M.Z.); (A.D.)
| | - Alina Aktanova
- Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya, 6300099 Novosibirsk, Russia; (A.A.); (V.K.)
| | - Maria Bykova
- Department of Medicine, Novosibirsk State University, 2, Pirogova Street, 630090 Novosibirsk, Russia;
| | - Mikhail Khvostov
- Institute of Organic Chemistry SB RAS, 9, Lavrentev Prospect, 630090 Novosibirsk, Russia;
| | - Aleksandr Dushkin
- Institute of Solid State Chemistry and Mechanochemistry, 18, Kutateladze, 630090 Novosibirsk, Russia; (V.E.); (M.Z.); (A.D.)
| | - Vladimir Kozlov
- Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya, 6300099 Novosibirsk, Russia; (A.A.); (V.K.)
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Abstract
PURPOSE OF REVIEW Allergen immunotherapy is the only recognized causal treatment for allergic disease that modulates the immune system toward a tolerogenic or desensitized state. Allergens or their derivative preparations are formulated with adjuvants of different origin and having diverse immunological functions, such as prolonged tissue release and specific immunomodulatory properties. In the last 2 decades, thanks to developments in the field of nanotechnology, more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. RECENT FINDINGS Nanomaterials possess unique and versatile properties which can be employed to develop drug carriers with safer profiles, better stability in physiological conditions and immunomodulatory properties. Nanoparticles can have an adjuvant effect per se or also when they are packed in structures whose physical-chemical properties can be handled in a way that also influences its release dynamics. In particular, it has been suggested that nanoparticle preparations can be put in complexes or loaded with allergens or allergenic extracts, opening the way to innovative paradigms. SUMMARY In this review, we analyze allergen/nanoparticle properties in terms of cytotoxicity, stability and immunogenic reaction in in-vitro and animal systems.
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Chipps BE, Murphy KR, Oppenheimer J. 2020 NAEPP Guidelines Update and GINA 2021-Asthma Care Differences, Overlap, and Challenges. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2021; 10:S19-S30. [PMID: 34718214 DOI: 10.1016/j.jaip.2021.10.032] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 09/29/2021] [Accepted: 10/14/2021] [Indexed: 11/17/2022]
Abstract
The 2020 National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group (NAEPP [2020 Focused Asthma Update]) guidelines and the Global Initiative for Asthma (GINA) 2021 strategy report are compared in this Rostrum article. The methodologies of each publication are described. Subsequently, 4 different selected pharmacological recommendations are compared in the 2 documents: step 1 for children 0 to 4 years of age with viral-induced wheezing, step 2 in ages 12 years and older with the intermittent use of inhaled corticosteroid, steps 3 and 4 with single-inhaler maintenance and reliever therapy with inhaled corticosteroids-formoterol (SMART), and steps 3, 4, and 5 with add-on long-acting muscarinic antagonist therapy. Nonpharmacological recommendations are also considered and contrasted, including for exhaled nitric oxide, environmental control, immunotherapy, and bronchial thermoplasty. Similarities and differences in these 2 documents are highlighted, and recommendations are made about harmonizing the approaches where possible.
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Affiliation(s)
- Bradley E Chipps
- Capital Allergy and Respiratory Disease Center, Sacramento, Calif.
| | - Kevin R Murphy
- Boys Town National Research Hospital, Section of Adult and Pediatric Allergy and Pediatric Pulmonary, Boystown, Neb
| | - John Oppenheimer
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ
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15
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Uchida T, Nakagome K, Iemura H, Naito E, Miyauchi S, Uchida Y, Soma T, Nagata M. Clinical evaluation of rush immunotherapy using house dust mite allergen in Japanese asthmatics. Asia Pac Allergy 2021; 11:e32. [PMID: 34386408 PMCID: PMC8331263 DOI: 10.5415/apallergy.2021.11.e32] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 07/08/2021] [Indexed: 11/28/2022] Open
Abstract
Background Allergen immunotherapy (AIT) is a specific treatment of administering clinically important allergens to patients who have allergic diseases. In Japan, the standardized house dust mite (HDM) allergen for subcutaneous immunotherapy (SCIT) was approved in 2015, and we then introduced rush-immunotherapy (rush-IT) using the standardized HDM allergen for HDM-sensitive asthmatics. However, little data are available on the safety and effectiveness of rush-HDM-IT, especially for Japanese asthmatics. Objective The objective of this study was to examine the safety and clinical effectiveness of rush-IT using the standardized HDM for HDM-sensitive Japanese asthmatics. Methods Thirteen HDM-sensitive asthmatics who received rush-HDM-IT and 12 HDM-sensitive asthmatic controls were enrolled. To evaluate the safety, the number of systemic reaction (SR) events, including anaphylaxis, was assessed. To evaluate the effectiveness, changes in the treatment step, dose of inhaled corticosteroid, and asthma control after rush-HDM-IT and the subsequent maintenance SCIT were assessed. Changes in the HDM-induced production of type 2 cytokines from peripheral blood mononuclear cells were also evaluated. Results Among the 12 patients who received rush-IT, 4 (30.7%) experienced a SR and 3 (23.1%) experienced anaphylaxis. However, the anaphylaxis was not severe (grade 3) in all cases, and they recovered in a short time. The treatment step of asthma was better and the dose of inhaled corticosteroid was lower in the rush-HDM-IT group than in the control group. The HDM-induced production of both interleukin (IL)-5 and IL-13 from peripheral blood mononuclear cells was significantly lower in the rush-HDM-IT group than in the control group. Conclusion Rush-HDM-IT can be performed relatively safely in Japanese asthmatics. Furthermore, rush-HDM-IT and the subsequent maintenance SCIT provided clinical improvement in asthma patients, and was accompanied by the suppression of HDM-specific Th2-mediated systemic immune responses.
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Affiliation(s)
- Takahiro Uchida
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Kazuyuki Nakagome
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Hidetoshi Iemura
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Erika Naito
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Sachiko Miyauchi
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Yoshitaka Uchida
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Tomoyuki Soma
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
| | - Makoto Nagata
- Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Saitama, Japan
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16
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Allergen Immunotherapy in Pediatric Respiratory Allergy. CURRENT TREATMENT OPTIONS IN ALLERGY 2021. [DOI: 10.1007/s40521-021-00280-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Abstract
Purpose of Review
Atopic diseases such as asthma and allergic rhinitis are highly prevalent in children. Common triggers include tree and grass pollens, house dust mites, molds, and animal dander. These diseases are most often treated symptomatically; however, many patients show partial or poor response and require long-term medication use. Allergen immunotherapy (AIT) stands as the only treatment modality that can alter the underlying disease process and potentially offer a cure. In this review article, we discuss the merits of AIT with particular emphasis on its efficacy and safety in pediatric patients. We also discuss the challenges for AIT implementation and present an overview of current research that aims at improving its applicability for the treatment of allergic diseases.
Recent Findings
Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are both safe and efficacious treatment options in children with allergic rhinitis and allergic asthma. Additionally, AIT has efficacy in preventing the development of asthma in children. Although there are clear advantages with AIT, there are challenges to overcome to optimize treatment. Solutions include improved diagnostics with pre-treatment biomarkers and molecular multiplex assays, biomarkers for prediction of response (e.g., basophil activation markers), improved allergen immunogenicity with the use of recombinant AIT, adjuvants, and allergoids, and lastly improved safety with the concurrent use of omalizumab.
Summary
AIT has shown safety and efficacy in major clinical trials for the treatment of allergic rhinitis and allergic asthma in children. AIT provides a curative treatment option for atopic disorders and should be considered in children with allergic rhinitis and allergic asthma. There are many continued advances being made in the field of allergy to further improve the safety and efficacy profile and shorten the duration of AIT treatment.
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17
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Nagy NA, de Haas AM, Geijtenbeek TBH, van Ree R, Tas SW, van Kooyk Y, de Jong EC. Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance. Front Immunol 2021; 12:674048. [PMID: 34054859 PMCID: PMC8155586 DOI: 10.3389/fimmu.2021.674048] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 04/26/2021] [Indexed: 12/15/2022] Open
Abstract
Dendritic cells (DCs) are paramount in initiating and guiding immunity towards a state of activation or tolerance. This bidirectional capacity of DCs sets them at the center stage for treatment of cancer and autoimmune or allergic conditions. Accordingly, many clinical studies use ex vivo DC vaccination as a strategy to boost anti-tumor immunity or to suppress immunity by including vitamin D3, NF-κB inhibitors or retinoic acid to create tolerogenic DCs. As harvesting DCs from patients and differentiating these cells in vitro is a costly and cumbersome process, in vivo targeting of DCs has huge potential as nanoparticulate platforms equipped with activating or tolerogenic adjuvants can modulate DCs in their natural environment. There is a rapid expansion of the choices of nanoparticles and activation- or tolerance-promoting adjuvants for a therapeutic vaccine platform. In this review we highlight the most recent nanomedical approaches aimed at inducing immune activation or tolerance via targeting DCs, together with novel fundamental insights into the mechanisms inherent to fostering anti-tumor or tolerogenic immunity.
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Affiliation(s)
- Noémi Anna Nagy
- Department of Experimental Immunology, Amsterdam University Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, Netherlands
| | - Aram M. de Haas
- Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Center, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Teunis B. H. Geijtenbeek
- Department of Experimental Immunology, Amsterdam University Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, Netherlands
| | - Ronald van Ree
- Department of Experimental Immunology, Amsterdam University Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, Netherlands
- Department of Otorhinolaryngology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Sander W. Tas
- Department of Experimental Immunology, Amsterdam University Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, Netherlands
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam Rheumatology and Immunology Center, University of Amsterdam, Amsterdam, Netherlands
| | - Yvette van Kooyk
- Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Center, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Esther C. de Jong
- Department of Experimental Immunology, Amsterdam University Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, Netherlands
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18
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Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, Dixon AE, Elward KS, Hartert T, Krishnan JA, Lemanske RF, Ouellette DR, Pace WD, Schatz M, Skolnik NS, Stout JW, Teach SJ, Umscheid CA, Walsh CG. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol 2020; 146:1217-1270. [PMID: 33280709 PMCID: PMC7924476 DOI: 10.1016/j.jaci.2020.10.003] [Citation(s) in RCA: 491] [Impact Index Per Article: 98.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 10/06/2020] [Indexed: 12/22/2022]
Abstract
The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders:A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality's (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format.
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Affiliation(s)
- Michelle M Cloutier
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Alan P Baptist
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Kathryn V Blake
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Edward G Brooks
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Tyra Bryant-Stephens
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Emily DiMango
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Anne E Dixon
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Kurtis S Elward
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Tina Hartert
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Jerry A Krishnan
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Robert F Lemanske
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Daniel R Ouellette
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Wilson D Pace
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Michael Schatz
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Neil S Skolnik
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - James W Stout
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Stephen J Teach
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Craig A Umscheid
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
| | - Colin G Walsh
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda
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19
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Hesse L, van Ieperen N, Petersen AH, Elberink JNGO, van Oosterhout AJM, Nawijn MC. High dose vitamin D 3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma. Sci Rep 2020; 10:20876. [PMID: 33257771 PMCID: PMC7705678 DOI: 10.1038/s41598-020-77947-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/19/2020] [Indexed: 12/14/2022] Open
Abstract
Allergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.
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Affiliation(s)
- Laura Hesse
- Department of Pathology and Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), University Medical Center Groningen (UMCG), Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, Internal Postcode EA52, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - N van Ieperen
- Department of Pathology and Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), University Medical Center Groningen (UMCG), Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, Internal Postcode EA52, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Arjen H Petersen
- Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - J N G Oude Elberink
- Division of Allergy, Department of Internal Medicine, University Medical Centre Groningen, Groningen, The Netherlands
| | - Antoon J M van Oosterhout
- Department of Pathology and Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), University Medical Center Groningen (UMCG), Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, Internal Postcode EA52, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Martijn C Nawijn
- Department of Pathology and Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), University Medical Center Groningen (UMCG), Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, Internal Postcode EA52, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
- Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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20
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Pali-Schöll I, DeBoer DJ, Alessandri C, Seida AA, Mueller RS, Jensen-Jarolim E. Formulations for Allergen Immunotherapy in Human and Veterinary Patients: New Candidates on the Horizon. Front Immunol 2020; 11:1697. [PMID: 32849594 PMCID: PMC7417425 DOI: 10.3389/fimmu.2020.01697] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 06/25/2020] [Indexed: 12/20/2022] Open
Abstract
Allergen immunotherapy is currently the only causal treatment for allergic diseases in human beings and animals. It aims to re-direct the immune system into a tolerogenic or desensitized state. Requirements include clinical efficacy, safety, and schedules optimizing patient or owner compliance. To achieve these goals, specific allergens can be formulated with adjuvants that prolong tissue deposition and support uptake by antigen presenting cells, and/or provide a beneficial immunomodulatory action. Here, we depict adjuvant formulations being investigated for human and veterinary allergen immunotherapy.
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Affiliation(s)
- Isabella Pali-Schöll
- University of Veterinary Medicine, Vienna, Austria.,Institute of Pathophysiology and Allergy Research, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Douglas J DeBoer
- Dermatology/Allergy Section, Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United States
| | | | - Ahmed Adel Seida
- Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Ralf S Mueller
- Centre for Clinical Veterinary Medicine, University of Munich, Munich, Germany
| | - Erika Jensen-Jarolim
- Institute of Pathophysiology and Allergy Research, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Vienna, Austria
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21
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Feng Z, Yi X, Hajavi J. New and old adjuvants in allergen-specific immunotherapy: With a focus on nanoparticles. J Cell Physiol 2020; 236:863-876. [PMID: 32657468 DOI: 10.1002/jcp.29941] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 07/01/2020] [Indexed: 12/19/2022]
Abstract
Allergic diseases have remarkably increased in recent years. Nowadays, efforts for curing and management of these disorders are an important concern worldwide. Allergen-specific immunotherapy (ASIT) has recently gained more attention as a means for the management of allergic diseases. Adjuvants or helper agents are materials applied for better stimulating and shifting of protective responses, and these belong to an extremely diverse collection of complexes. The main function of adjuvants includes acting as depot foundations, transferring vehicles, and immunostimulators. Immunostimulatory adjuvants have gained increasing attention for ASIT. In this regard, the present study provides a review of old and new adjuvants used in allergen immunotherapy.
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Affiliation(s)
- Zhongtao Feng
- Department of Clinical Laboratory, Jining No.1 People's Hospital, Jining, China
| | - Xin Yi
- Department of Clinical Laboratory, Jining No.1 People's Hospital, Jining, China
| | - Jafar Hajavi
- Department of Basic Sciences, Faculty of Allied Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
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22
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Di Gioacchino M, Petrarca C, Gatta A, Scarano G, Farinelli A, Della Valle L, Lumaca A, Del Biondo P, Paganelli R, Di Giampaolo L. Nanoparticle-based immunotherapy: state of the art and future perspectives. Expert Rev Clin Immunol 2020; 16:513-525. [PMID: 32343153 DOI: 10.1080/1744666x.2020.1762572] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capable per se of immune-modulating activity, or as carriers for molecules to be transported to a specific target, eventually loaded with specific ligands favoring specific uptake. AREAS COVERED The review focuses on experimental use of NPs as adjuvants/carriers for allergen immunotherapy (AIT). Human clinical trials conducted so far are discussed. EXPERT OPINION Results of experimental studies and recent clinical trials support the use of NPs as carrier/adjuvant in AIT. Comparisons between NP-based and classical AIT are needed, to show the usefulness of the NP-based approach. However, there are still unsolved problems: the persistence of non-degradable NPs with possible toxicological consequences, and the formation of the protein corona around the NPs, which could alter their activity and fate. Virus-like particles seem the most promising NPs for allergy treatment, as for other vaccines. Over the next decade, NP-based AIT will be largely used to treat allergic disorders.
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Affiliation(s)
- Mario Di Gioacchino
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Leonardo Da Vinci, University , Chieti, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Claudia Petrarca
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy
| | - Alessia Gatta
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy
| | - Gilda Scarano
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Anila Farinelli
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Loredana Della Valle
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Arianna Lumaca
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Pietro Del Biondo
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Roberto Paganelli
- Department of Medicine and Science of Ageing, G. d'Annunzio University , Chieti, Pescara, Italy.,Department of Medicine and Science of Ageing, Specialization School of Allergy and Clinical Immunology, G. d'Annunzio University Chieti-Pescara , Italy
| | - Luca Di Giampaolo
- Department of Medical Oral and Biotechnological Sciences, G. d'Annunzio University , Chieti, Pescara, Italy
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23
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Alvaro-Lozano M, Akdis CA, Akdis M, Alviani C, Angier E, Arasi S, Arzt-Gradwohl L, Barber D, Bazire R, Cavkaytar O, Comberiati P, Dramburg S, Durham SR, Eifan AO, Forchert L, Halken S, Kirtland M, Kucuksezer UC, Layhadi JA, Matricardi PM, Muraro A, Ozdemir C, Pajno GB, Pfaar O, Potapova E, Riggioni C, Roberts G, Rodríguez Del Río P, Shamji MH, Sturm GJ, Vazquez-Ortiz M. EAACI Allergen Immunotherapy User's Guide. Pediatr Allergy Immunol 2020; 31 Suppl 25:1-101. [PMID: 32436290 PMCID: PMC7317851 DOI: 10.1111/pai.13189] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.
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Affiliation(s)
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.,Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
| | - Mubeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Cherry Alviani
- The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, UK.,Clinical and Experimental Sciences and Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Elisabeth Angier
- Primary Care and Population Sciences, University of Southampton, Southampton, UK
| | - Stefania Arasi
- Pediatric Allergology Unit, Department of Pediatric Medicine, Bambino Gesù Children's research Hospital (IRCCS), Rome, Italy
| | - Lisa Arzt-Gradwohl
- Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria
| | - Domingo Barber
- School of Medicine, Institute for Applied Molecular Medicine (IMMA), Universidad CEU San Pablo, Madrid, Spain.,RETIC ARADYAL RD16/0006/0015, Instituto de Salud Carlos III, Madrid, Spain
| | - Raphaëlle Bazire
- Allergy Department, Hospital Infantil Niño Jesús, ARADyAL RD16/0006/0026, Madrid, Spain
| | - Ozlem Cavkaytar
- Department of Paediatric Allergy and Immunology, Faculty of Medicine, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
| | - Pasquale Comberiati
- Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.,Department of Clinical and Experimental Medicine, Section of Paediatrics, University of Pisa, Pisa, Italy
| | - Stephanie Dramburg
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Medical University, Berlin, Germany
| | - Stephen R Durham
- Immunomodulation and Tolerance Group; Allergy and Clinical Immunology, Section of Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, London, UK.,the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK
| | - Aarif O Eifan
- Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospitals NHS Foundation Trust, London, UK
| | - Leandra Forchert
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Medical University, Berlin, Germany
| | - Susanne Halken
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark
| | - Max Kirtland
- Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
| | - Umut C Kucuksezer
- Aziz Sancar Institute of Experimental Medicine, Department of Immunology, Istanbul University, Istanbul, Turkey
| | - Janice A Layhadi
- Immunomodulation and Tolerance Group; Allergy and Clinical Immunology, Section of Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, London, UK.,the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.,Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
| | - Paolo Maria Matricardi
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Medical University, Berlin, Germany
| | - Antonella Muraro
- The Referral Centre for Food Allergy Diagnosis and Treatment Veneto Region, Department of Women and Child Health, University of Padua, Padua, Italy
| | - Cevdet Ozdemir
- Institute of Child Health, Department of Pediatric Basic Sciences, Istanbul University, Istanbul, Turkey.,Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy and Immunology, Istanbul University, Istanbul, Turkey
| | | | - Oliver Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
| | - Ekaterina Potapova
- Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charité Medical University, Berlin, Germany
| | - Carmen Riggioni
- Pediatric Allergy and Clinical Immunology Service, Institut de Reserca Sant Joan de Deú, Barcelona, Spain
| | - Graham Roberts
- The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, UK.,NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.,Paediatric Allergy and Respiratory Medicine (MP803), Clinical & Experimental Sciences & Human Development in Health Academic Units University of Southampton Faculty of Medicine & University Hospital Southampton, Southampton, UK
| | | | - Mohamed H Shamji
- Immunomodulation and Tolerance Group; Allergy and Clinical Immunology, Section of Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, London, UK.,the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK
| | - Gunter J Sturm
- Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria
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24
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Thoms F, Haas S, Erhart A, Nett CS, Rüfenacht S, Graf N, Strods A, Patil G, Leenadevi T, Fontaine MC, Toon LA, Jennings GT, Senti G, Kündig TM, Bachmann MF. Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners. Viruses 2020; 12:v12030288. [PMID: 32155887 PMCID: PMC7150904 DOI: 10.3390/v12030288] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 02/20/2020] [Accepted: 02/26/2020] [Indexed: 12/23/2022] Open
Abstract
An innovative approach was tested to treat cat allergy in humans by vaccinating cats with Fel-CuMV (HypoCatTM), a vaccine against the major cat allergen Fel d 1 based on virus-like particles derived from cucumber mosaic virus (CuMV-VLPs). Upon vaccination, cats develop neutralizing antibodies against the allergen Fel d 1, which reduces the level of reactive allergen, thus lowering the symptoms or even preventing allergic reactions in humans. The combined methodological field study included ten cat-allergic participants who lived together with their cats (n = 13), that were immunized with Fel-CuMV. The aim was to determine methods for measuring a change in allergic symptoms. A home-based provocation test (petting time and organ specific symptom score (OSSS)) and a general weekly (or monthly) symptom score (G(W)SS) were used to assess changes in allergic symptoms. The petting time until a pre-defined level of allergic symptoms was reached increased already early after vaccination of the cats and was apparent over the course of the study. In addition, the OSSS after provocation and G(W)SS recorded a persistent reduction in symptoms over the study period and could serve for long-term assessment. Hence, the immunization of cats with HypoCatTM (Fel-CuMV) may have a positive impact on the cat allergy of the owner, and changes could be assessed by the provocation test as well as G(W)SS.
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Affiliation(s)
- Franziska Thoms
- Department of Dermatology, Zurich University Hospital, Wagistrasse 12, 8952 Schlieren/Zurich, Switzerland; (F.T.); (S.H.); (G.T.J.)
- HypoPet AG, Moussonstrasse 2, 8091 Zurich, Switzerland
| | - Stefanie Haas
- Department of Dermatology, Zurich University Hospital, Wagistrasse 12, 8952 Schlieren/Zurich, Switzerland; (F.T.); (S.H.); (G.T.J.)
- HypoPet AG, Moussonstrasse 2, 8091 Zurich, Switzerland
| | - Aline Erhart
- Clinical Trials Center Zurich, University Hospital Zurich, Moussonstrasse 2, 8044 Zurich, Switzerland;
| | - Claudia S. Nett
- vetderm.ch, Ennetseeklink für Kleintiere, Rothusstrasse 2, 6331 Hünenberg, Switzerland;
| | - Silvia Rüfenacht
- dermaVet, Tierklinik Aarau West AG, Muhenstrasse 56, 5036 Oberentfelden, Switzerland;
| | - Nicole Graf
- Graf Biostatistics, Amelenweg 5, 8400 Winterthur, Switzerland;
| | - Arnis Strods
- Benchmark Animal Health, Benchmark Holdings Plc, 8 Smithy Wood Dr, Sheffield S35 1QN, UK; (A.S.); (G.P.); (T.L.); (M.C.F.); (L.A.T.)
| | - Gauravraj Patil
- Benchmark Animal Health, Benchmark Holdings Plc, 8 Smithy Wood Dr, Sheffield S35 1QN, UK; (A.S.); (G.P.); (T.L.); (M.C.F.); (L.A.T.)
| | - Thonur Leenadevi
- Benchmark Animal Health, Benchmark Holdings Plc, 8 Smithy Wood Dr, Sheffield S35 1QN, UK; (A.S.); (G.P.); (T.L.); (M.C.F.); (L.A.T.)
| | - Michael C. Fontaine
- Benchmark Animal Health, Benchmark Holdings Plc, 8 Smithy Wood Dr, Sheffield S35 1QN, UK; (A.S.); (G.P.); (T.L.); (M.C.F.); (L.A.T.)
| | - Lindsey A. Toon
- Benchmark Animal Health, Benchmark Holdings Plc, 8 Smithy Wood Dr, Sheffield S35 1QN, UK; (A.S.); (G.P.); (T.L.); (M.C.F.); (L.A.T.)
| | - Gary T. Jennings
- Department of Dermatology, Zurich University Hospital, Wagistrasse 12, 8952 Schlieren/Zurich, Switzerland; (F.T.); (S.H.); (G.T.J.)
- HypoPet AG, Moussonstrasse 2, 8091 Zurich, Switzerland
| | - Gabriela Senti
- Director Research and Education, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland;
| | - Thomas M. Kündig
- Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland;
| | - Martin F. Bachmann
- Department of Immunology, Inselspital, University of Bern, Salihaus 2, 3007 Bern, Switzerland
- Jenner Institute, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7BN, UK
- Correspondence:
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25
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Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners. Viruses 2020. [PMID: 32155887 DOI: 10.3390/v12030288.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
An innovative approach was tested to treat cat allergy in humans by vaccinating cats with Fel-CuMV (HypoCatTM), a vaccine against the major cat allergen Fel d 1 based on virus-like particles derived from cucumber mosaic virus (CuMV-VLPs). Upon vaccination, cats develop neutralizing antibodies against the allergen Fel d 1, which reduces the level of reactive allergen, thus lowering the symptoms or even preventing allergic reactions in humans. The combined methodological field study included ten cat-allergic participants who lived together with their cats (n = 13), that were immunized with Fel-CuMV. The aim was to determine methods for measuring a change in allergic symptoms. A home-based provocation test (petting time and organ specific symptom score (OSSS)) and a general weekly (or monthly) symptom score (G(W)SS) were used to assess changes in allergic symptoms. The petting time until a pre-defined level of allergic symptoms was reached increased already early after vaccination of the cats and was apparent over the course of the study. In addition, the OSSS after provocation and G(W)SS recorded a persistent reduction in symptoms over the study period and could serve for long-term assessment. Hence, the immunization of cats with HypoCatTM (Fel-CuMV) may have a positive impact on the cat allergy of the owner, and changes could be assessed by the provocation test as well as G(W)SS.
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26
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Agache I, Lau S, Akdis CA, Smolinska S, Bonini M, Cavkaytar O, Flood B, Gajdanowicz P, Izuhara K, Kalayci O, Mosges R, Palomares O, Papadopoulos NG, Sokolowska M, Angier E, Fernandez‐Rivas M, Pajno G, Pfaar O, Roberts G, Ryan D, Sturm GJ, Ree R, Varga EM, Wijk RG, Yepes‐Nuñez J, Jutel M. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma. Allergy 2019; 74:855-873. [PMID: 31095767 DOI: 10.1111/all.13749] [Citation(s) in RCA: 178] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/12/2019] [Indexed: 12/14/2022]
Abstract
Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).
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Affiliation(s)
- Ioana Agache
- Faculty of Medicine Department of Allergy and Clinical Immunology Transylvania University Brasov Brasov Romania
| | - Susanne Lau
- Department for Pediatric Pneumology, Immunology and Intensive Care Charité Universität Medizin Berlin Germany
| | - Cezmi A. Akdis
- University of Zürich Swiss Institute of Allergy and Asthma Research (SIAF) Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education (CK‐CARE) Davos Switzerland
| | - Sylwia Smolinska
- Department of Clinical Immunology Wroclaw Medical University Wroclaw Poland
- “ALL‐MED” Medical Research Institute Wroclaw Poland
| | - Matteo Bonini
- National Heart and Lung Institute (NHLI) Royal Brompton Hospital & Imperial College London UK
| | - Ozlem Cavkaytar
- Faculty of Medicine Department of Pediatric Allergy Istanbul Medeniyet University Goztepe Training and Research Hospital Istanbul Turkey
| | - Breda Flood
- European Federation of Allergy and Airways Diseases, Patients Association Brussels Belgium
| | - Pawe Gajdanowicz
- Department of Clinical Immunology Wroclaw Medical University Wroclaw Poland
| | | | - Omer Kalayci
- Hacettepe University School of Medicine Ankara Turkey
| | - Ralph Mosges
- Universität zu Koln Institute of Medical Statistics, Informatics and Epidemiology (IMSIE) Koln Germany
| | - Oscar Palomares
- Department of Biochemistry and Molecular Biology Complutense University of Madrid Madrid Spain
| | - Nikolaos G. Papadopoulos
- Division of Infection, Immunity and respiratory medicine University of Manchester Manchester UK
- Allergy Department 2nd Pediatric Clinic University of Athens Athens Greece
| | - Milena Sokolowska
- University of Zürich Swiss Institute of Allergy and Asthma Research (SIAF) Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education (CK‐CARE) Davos Switzerland
| | | | | | - Giovanni Pajno
- Allergy Unit Department of Pediatrics University of Messina Messina Italy
| | - Oliver Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery Section of Rhinology and Allergy University Hospital Marburg Philipps‐Universität Marburg Marburg Germany
| | - Graham C. Roberts
- The David Hide Asthma and Allergy Research Centre St Mary's Hospital Newport Isle of Wight UK
- NIHR Biomedical Research Centre University Hospital Southampton NHS Foundation Trust Southampton UK
- Faculty of Medicine University of Southampton Southampton UK
| | - Dermot Ryan
- Usher Institute of Population Health Sciences and Informatics University of Edinburgh Edinburgh UK
- Asthma UK Centre for Applied Research The University of Edinburgh Edinburgh UK
| | - Gunter J. Sturm
- Department of Dermatology and Venerology Medical University of Graz Graz Austria
- Outpatient Allergy Clinic Reumannplaz Vienna Austria
| | - Ronald Ree
- Department of Experimental Immunology Academic Medical Center University of Amsterdam Amsterdam The Netherlands
- Department of Otorhinolaryngology Academic Medical Center University of Amsterdam Amsterdam The Netherlands
| | - Eva M. Varga
- Department of Pediatric and Adolescent Medicine Respiratory and Allergic Disease Division Medical University of Graz Graz Austria
| | - Roy Gerth Wijk
- Section of Allergology Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands
| | | | - Marek Jutel
- Department of Clinical Immunology Wroclaw Medical University Wroclaw Poland
- “ALL‐MED” Medical Research Institute Wroclaw Poland
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27
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Knauer N, Pashkina E, Apartsin E. Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins. Pharmaceutics 2019; 11:E91. [PMID: 30795556 PMCID: PMC6410174 DOI: 10.3390/pharmaceutics11020091] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 02/18/2019] [Accepted: 02/19/2019] [Indexed: 12/17/2022] Open
Abstract
Supramolecular chemistry holds great potential for the design of versatile and safe carriers for therapeutic proteins and peptides. Nanocarriers can be designed to meet specific criteria for given application (exact drug, administration route, target tissue, etc.). However, alterations in the topology of formulation components can drastically change their activity. This is why the supramolecular topology of therapeutic nanoconstructions has to be considered. Herein, we discuss several topological groups used for the design of nanoformulations for peptide and protein delivery: modification of polypeptide chains by host-guest interactions; packaging of proteins and peptides into liposomes; complexation and conjugation with dendrimers. Each topological type has its own advantages and disadvantages, so careful design of nanoformulations is needed. Ideally, each case where nanomedicine is needed requires a therapeutic construction specially created for that taking into account features of the administration route, target tissue, or organ, properties of a drug, its bioavailability, etc. The wide number of studies in the field of protein delivery by supramolecular and nanocarriers for proteins and peptides evidence their increasing potential for different aspects of the innovative medicine. Although significant progress has been achieved in the field, there are several remaining challenges to be overcome in future.
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Affiliation(s)
- Nadezhda Knauer
- Research Institute of Fundamental and Clinical Immunology, 14, Yadrinthevskaya str., 630099 Novosibirsk, Russia.
| | - Ekaterina Pashkina
- Research Institute of Fundamental and Clinical Immunology, 14, Yadrinthevskaya str., 630099 Novosibirsk, Russia.
| | - Evgeny Apartsin
- Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev ave., 630090 Novosibirsk, Russia.
- Department of Natural Sciences, Novosibirsk State University, 2, Pirogov str., 630090 Novosibirsk, Russia.
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28
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Ramesh M, Karagic M. New modalities of allergen immunotherapy. Hum Vaccin Immunother 2018; 14:2848-2863. [PMID: 30183485 PMCID: PMC6343630 DOI: 10.1080/21645515.2018.1502126] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 06/27/2018] [Accepted: 07/13/2018] [Indexed: 10/28/2022] Open
Abstract
Allergen immunotherapy is a rapidly evolving field. Although subcutaneous immunotherapy has been practiced for over a hundred years, improved understanding of the underlying immunological mechanisms has led to the development of new, efficacious and better tolerated allergen-derivatives, adjuvants and encapsulated allergens. Diverse routes of allergen immunotherapy - oral, sublingual, epicutanoeus and intralymphatic - are enabling immunotherapy for anaphylactic food allergies and pollen-food allergy syndrome, while improving the tolerability and effectiveness of aeroallergen immunotherapy. The addition of Anti-IgE therapy decreases adverse effects of subcutaneous and oral immunotherapy.
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29
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Gunawardana NC, Durham SR. New approaches to allergen immunotherapy. Ann Allergy Asthma Immunol 2018; 121:293-305. [PMID: 30025907 DOI: 10.1016/j.anai.2018.07.014] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 07/10/2018] [Accepted: 07/10/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE New insights into mechanisms should enable strategic improvement of allergen immunotherapy, aiming to make it safer, faster, more effective, and able to induce long-term tolerance. We review novel approaches with potential to translate into clinical use. DATA SOURCES Database searches were conducted in PubMed, Scopus, and Google Scholar. STUDY SELECTIONS Search terms were based on current and novel approaches in immunotherapy. Literature was selected primarily from recent randomized double-blinded placebo-controlled trials and meta-analyses. RESULTS Alum, microcrystalline tyrosine, and calcium phosphate are adjuvants in current use. Toll-like receptor-4 agonists combined with allergen have potential to shorten duration of treatment. Other novel adjuvants, nanoparticles, and virus-like particles in combination with allergen have shown early promise. Omalizumab lessens systemic side effects but does not improve efficacy. Intralymphatic immunotherapy for aeroallergens, epicutaneous immunotherapy for food allergens, and use of modified allergens (allergoids), recombinant allergens (and hypoallergenic variants), and T- and B-cell peptide approaches have shown evidence of efficacy and permitted shortened courses but have only rarely been compared with conventional extracts. CONCLUSION Novel routes of immunotherapy, use of modified allergens, and combination of allergens with immunostimulatory adjuvants or immune modifiers have been developed to augment downregulation of T-helper cell type 2 immunity and/or induce "protective" blocking antibodies. Although these strategies have permitted shortened courses, confirmatory phase 3 trials are required to confirm efficacy and safety and head-to-head trials are required for comparative efficacy. Currently, subcutaneous and sublingual immunotherapies using in-house standardized crude extracts remain the only approaches proved to induce long-term tolerance.
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Affiliation(s)
- Natasha C Gunawardana
- Imperial College London, London, United Kingdom; Royal Brompton and Harefield Hospitals, NHS Foundation Trust, London, United Kingdom
| | - Stephen R Durham
- Imperial College London, London, United Kingdom; Royal Brompton and Harefield Hospitals, NHS Foundation Trust, London, United Kingdom.
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30
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Abstract
PURPOSE OF REVIEW During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. RECENT FINDINGS In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.
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31
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Dhami S, Kakourou A, Asamoah F, Agache I, Lau S, Jutel M, Muraro A, Roberts G, Akdis CA, Bonini M, Cavkaytar O, Flood B, Gajdanowicz P, Izuhara K, Kalayci Ö, Mosges R, Palomares O, Pfaar O, Smolinska S, Sokolowska M, Asaria M, Netuveli G, Zaman H, Akhlaq A, Sheikh A. Allergen immunotherapy for allergic asthma: A systematic review and meta-analysis. Allergy 2017; 72:1825-1848. [PMID: 28543086 DOI: 10.1111/all.13208] [Citation(s) in RCA: 216] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. METHODS We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses. RESULTS 98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95% CI -1.66, -0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95% CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI -0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. CONCLUSIONS AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness.
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Affiliation(s)
- S. Dhami
- Evidence-Based Health Care Ltd; Edinburgh UK
| | - A. Kakourou
- Department of Hygiene and Epidemiology; University of Ioannina School of Medicine; Ioannina Greece
| | - F. Asamoah
- Centre for Environmental and Preventive Medicine; Wolfson Institute of Preventive Medicine Barts and the London School of Medicine and Dentistry; Queen Mary University of London; London UK
| | - I. Agache
- Faculty of Medicine; Department of Allergy and Clinical Immunology; Transylvania University Brasov; Brasov Romania
| | - S. Lau
- Department of Pediatric Pneumology and Immunology; Charité Universitätsmedizin; Berlin Germany
| | - M. Jutel
- Wroclaw Medical University; Wroclaw Poland
- ALL-MED Medical Research Institute; Wroclaw Poland
| | - A. Muraro
- Food Allergy Referral Centre Veneto Region; University Hospital of Padua; Padua Italy
| | - G. Roberts
- The David Hide Asthma and Allergy Research Centre; St Mary's Hospital; Newport UK
- NIHR Biomedical Research Centre; University Hospital Southampton NHS Foundation Trust; Southampton UK
- Faculty of Medicine; University of Southampton; Southampton UK
| | - C. A. Akdis
- Swiss Institute for Allergy and Asthma Research; Christine Kühne-Center for Allergy Research and Education (CK-CARE); Davos Switzerland
| | - M. Bonini
- National Heart and Lung Institute; Imperial College London; London UK
| | - O. Cavkaytar
- Department of Allergy and Clinical Immunology; Sami Ulus Women's & Children's Diseases Training and Research Hospital; Ankara Turkey
- Department of Pediatric Allergy and Immunology; Ulus Women's & Children's Diseases Training and Research Hospital; Ankara Turkey
| | - B. Flood
- European Federation of Allergy and Airways Diseases Patients Association; Brussels Belgium
| | | | | | | | - R. Mosges
- Institute of Medical Statistics, Informatics and Epidemiology (IMSIE); University of Cologne; Köln Germany
| | - O. Palomares
- Department of Biochemistry and Molecular Biology; Complutense University of Madrid; Madrid Spain
| | - O. Pfaar
- Department of Otorhinolaryngology, Head and Neck Surgery; Universitätsmedizin Mannheim; Medical Faculty Mannheim; Heidelberg University; Mannheim Germany
- Center for Rhinology and Allergology; Wiesbaden Germany
| | - S. Smolinska
- Wroclaw Medical University; Wroclaw Poland
- ALL-MED Medical Research Institute; Wroclaw Poland
| | - M. Sokolowska
- Swiss Institute for Allergy and Asthma Research; Christine Kühne-Center for Allergy Research and Education (CK-CARE); Davos Switzerland
| | - M. Asaria
- Centre for Health Economics; University of York; York UK
| | - G. Netuveli
- Institute for Health and Human Development; University of East London; London UK
| | - H. Zaman
- Bradford School of Pharmacy; Bradford UK
| | - A. Akhlaq
- Health and Hospital Management; Institute of Business Management; Karachi Pakistan
| | - A. Sheikh
- Asthma UK Centre for Applied Research; The University of Edinburgh; Edinburgh UK
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Aliu H, Rask C, Brimnes J, Andresen TL. Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen. Int J Nanomedicine 2017; 12:8377-8388. [PMID: 29200850 PMCID: PMC5702530 DOI: 10.2147/ijn.s137033] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.
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Affiliation(s)
- Have Aliu
- Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm.,Department of Micro- and Nanotechnology, Technical University of Denmark.,Center for Nanomedicine and Theranostics, Technical University of Denmark, Kgs Lyngby, Denmark
| | - Carola Rask
- Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm
| | - Jens Brimnes
- Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm
| | - Thomas Lars Andresen
- Department of Micro- and Nanotechnology, Technical University of Denmark.,Center for Nanomedicine and Theranostics, Technical University of Denmark, Kgs Lyngby, Denmark
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Moingeon P, Lombardi V, Baron-Bodo V, Mascarell L. Enhancing Allergen-Presentation Platforms for Sublingual Immunotherapy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2017; 5:23-31. [PMID: 28065340 DOI: 10.1016/j.jaip.2016.07.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 07/22/2016] [Accepted: 07/25/2016] [Indexed: 01/24/2023]
Abstract
Sublingual immunotherapy (SLIT) relies on high doses of allergens to treat patients with type I allergies. Although SLIT is commonly performed without any adjuvant or delivery system, allergen(s) could be further formulated with allergen-presentation platforms to better target oral dendritic cells eliciting regulatory immune responses. Improving the availability of allergens to the immune system should enhance SLIT efficacy, while allowing to decrease allergen dosing. Herein, we present an overview of adjuvants and vector systems that have been, or could be, considered as candidate allergen-presentation platforms for the sublingual route. Such platforms encompass adjuvants capable of stimulating allergen-specific TH1 and/or regulatory CD4+ T-cell responses, including 1,25-dihydroxy vitamin D3, glucocorticoids, Toll-like receptor ligands as well as selected bacterial probiotic strains. A limiting factor for SLIT efficacy is the number of dendritic cells capturing the allergens in the upper layers of oral tissues. Thus, adsorption or encapsulation of the allergen(s) within mucoadhesive particulate vector (or delivery) systems also has the potential to significantly enhance SLIT efficacy due to a facilitated allergen uptake by tolerogenic oral dendritic cells.
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Affiliation(s)
- P Moingeon
- Research and Development, Stallergenes Greer, Antony, France.
| | - V Lombardi
- Research and Development, Stallergenes Greer, Antony, France
| | - V Baron-Bodo
- Research and Development, Stallergenes Greer, Antony, France
| | - L Mascarell
- Research and Development, Stallergenes Greer, Antony, France
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Liu JL, Ning WX, Li SX, Xu YC, Wu L, Wang YS, Xu XF, Jiang Y, Sheng YJ, Zhou YL, Wang JH, Tang LF, Chen ZM. The safety profile of subcutaneous allergen immunotherapy in children with asthma in Hangzhou, East China. Allergol Immunopathol (Madr) 2017. [PMID: 28629672 DOI: 10.1016/j.aller.2017.04.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND The aim of the current study is to evaluate the prevalence, severity and possible risk factors of systemic reactions (SRs) to subcutaneous allergen immunotherapy (SCIT) in children and adolescents with asthma in Hangzhou, east China's Zhejiang province. METHODS From January 2011 to December 2016, this survey analysed the SCIT-related SRs involving 429 patients (265 children and 134 adolescents) affected by allergic asthma. Recorded data included demographics, diagnosis, patient statuses, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. RESULTS All patients finished the initial phase and six patients withdrew during the maintenance phase. There were 2.59% (328/12,655) SRs in all injections (3.28% in children and 1.47% in adolescents); 15.62% (67/429) patients experienced SRs (18.49% children and 10.98% adolescents). There were 54.57% SRs of grade 1; 42.37% SRs of grade 2; 3.05% SRs of grade 3; and no grades 4 or grade 5 SRs occurred in patients. Most reactions were mild, and were readily controlled by immediate emergency treatment. There was no need for hospitalisation. The occurrence of SRs was significantly higher in children than that in adolescents (p<0.01). A higher ratio of SRs was found among patients with moderate asthma. CONCLUSION This retrospective survey showed that properly-conducted SCIT was a safe treatment for children and adolescents with asthma in Hangzhou, East China. Children and patients with moderate asthma may be prone to develop SRs.
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Zhong C, Yang W, Li Y, Zou L, Deng Z, Liu M, Huang X. Clinical evaluation for sublingual immunotherapy with Dermatophagoides farinae drops in adult patients with allergic asthma. Ir J Med Sci 2017; 187:441-446. [PMID: 29032417 DOI: 10.1007/s11845-017-1685-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 10/03/2017] [Indexed: 02/01/2023]
Abstract
PURPOSE The efficacy and safety of sublingual immunotherapy (SLIT) in house dust mite-induced allergic asthma (AA) have yet to be firmly established, especially in adult patients. Our objective is to evaluate the efficacy of SLIT with Dermatophagoides farinae drops in adult patients with AA. METHODS One hundred and thirty-four adult patient data with house dust mite (HDM)-induced AA who had been treated for 2 years were collected. These patient data that we collected were divided into the SLIT group (n = 85) and control group (n = 49). All patients were treated with low to moderate dose of inhaled glucocorticoid and long-acting β2 agonists. Patients in the SLIT group were further treated with D. farinae drops. Clinical scores including the total asthma symptom score (TASS), total asthma medicine score (TAMS), asthma control test (ACT), and peak flow percentage (PEF%) were assessed before treatment and at yearly visits. The presence of adverse events (AEs) were recorded once a month. RESULTS Before treatment, the PEF% in the SLIT group was significantly lower than that in the control group (p < 0.05). After 2 years, both treatments were effective in the clinical scores when compared with baseline values (all p < 0.001). Meanwhile, the SLIT group showed significantly lower TASS and TAMS (all p < 0.001) and higher ACT (p < 0.001) and PEF% (p < 0.05) when compared with the control group. No severe systemic AEs were reported. CONCLUSIONS SLIT with D. farinae drops plus pharmacotherapy is more effective than routine drug treatment in adult patients with AA.
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Affiliation(s)
- C Zhong
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China.
| | - W Yang
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China
| | - Y Li
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China
| | - L Zou
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China
| | - Z Deng
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China
| | - M Liu
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China
| | - X Huang
- Department of Respiratory, Wuzhou Red Cross Hospital, No.1-3 Xinxingyi road, Dieshan district, Wuzhou, 543002, China
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Pohlit H, Bellinghausen I, Frey H, Saloga J. Recent advances in the use of nanoparticles for allergen-specific immunotherapy. Allergy 2017; 72:1461-1474. [PMID: 28474379 DOI: 10.1111/all.13199] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2017] [Indexed: 12/28/2022]
Abstract
The number of patients suffering from allergic asthma and rhinoconjunctivitis has increased dramatically within the last decades. Allergen-specific immunotherapy (AIT) is the only available cause-oriented therapy so far. AIT reduces symptoms, but has also a disease-modifying effect. Disadvantages are a long-lasting procedure, and in a few cases potential systemic adverse reactions. Encapsulation of allergens or DNA vaccines into nanostructures may provide advantages compared to the conventional AIT with noncapsulated allergen extracts: The protein/DNA molecule can be protected from degradation, higher local concentrations and targeted delivery to the site of action appear possible, and most importantly, recognition of encapsulated allergen by the immune system, especially by IgE antibodies, is prevented. AIT with nanoparticles (NPs) may offer a safer and potentially more efficient way of treatment for allergic diseases. In this review, we summarize the use of biodegradable NPs consisting of synthetic or natural polymers, liposomes, and virus-like particles as well as nonbiodegradable NPs like dendrimers, and carbon- or metal-based NPs for AIT. More or less successful applications of these NPs in prophylactic as well as therapeutic vaccination approaches in rodents or other animals as well as first human clinical trials are discussed in detail.
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Affiliation(s)
- H. Pohlit
- Department of Dermatology; University Medical Center of the Johannes Gutenberg University Mainz; Mainz Germany
- Institute of Organic Chemistry; Johannes Gutenberg-University Mainz; Mainz Germany
- Graduate School of Excellence Materials Science in Mainz; Johannes Gutenberg-University Mainz; Mainz Germany
| | - I. Bellinghausen
- Department of Dermatology; University Medical Center of the Johannes Gutenberg University Mainz; Mainz Germany
| | - H. Frey
- Institute of Organic Chemistry; Johannes Gutenberg-University Mainz; Mainz Germany
| | - J. Saloga
- Department of Dermatology; University Medical Center of the Johannes Gutenberg University Mainz; Mainz Germany
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Silva AL, Peres C, Conniot J, Matos AI, Moura L, Carreira B, Sainz V, Scomparin A, Satchi-Fainaro R, Préat V, Florindo HF. Nanoparticle impact on innate immune cell pattern-recognition receptors and inflammasomes activation. Semin Immunol 2017; 34:3-24. [PMID: 28941640 DOI: 10.1016/j.smim.2017.09.003] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/10/2017] [Accepted: 09/11/2017] [Indexed: 12/19/2022]
Abstract
Nanotechnology-based strategies can dramatically impact the treatment, prevention and diagnosis of a wide range of diseases. Despite the unprecedented success achieved with the use of nanomaterials to address unmet biomedical needs and their particular suitability for the effective application of a personalized medicine, the clinical translation of those nanoparticulate systems has still been impaired by the limited understanding on their interaction with complex biological systems. As a result, unexpected effects due to unpredicted interactions at biomaterial and biological interfaces have been underlying the biosafety concerns raised by the use of nanomaterials. This review explores the current knowledge on how nanoparticle (NP) physicochemical and surface properties determine their interactions with innate immune cells, with particular attention on the activation of pattern-recognition receptors and inflammasome. A critical perspective will additionally address the impact of biological systems on the effect of NP on immune cell activity at the molecular level. We will discuss how the understanding of the NP-innate immune cell interactions can significantly add into the clinical translation by guiding the design of nanomedicines with particular effect on targeted cells, thus improving their clinical efficacy while minimizing undesired but predictable toxicological effects.
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Affiliation(s)
- Ana Luísa Silva
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Carina Peres
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - João Conniot
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Ana I Matos
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Liane Moura
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Bárbara Carreira
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Vanessa Sainz
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Anna Scomparin
- Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel and dSagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Ronit Satchi-Fainaro
- Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel and dSagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Véronique Préat
- Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
| | - Helena F Florindo
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
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Clinical and immunological effect of subcutaneous immunotherapy in allergic asthma. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2017. [DOI: 10.1016/j.ejcdt.2016.10.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Tortajada-Girbés M, Mesa Del Castillo M, Larramona H, Lucas JM, Álvaro M, Tabar AI, Jerez MJ, Martínez-Cañavate A. Evidence in immunotherapy for paediatric respiratory allergy: Advances and recommendations. Allergol Immunopathol (Madr) 2016; 44 Suppl 1:1-32. [PMID: 27776895 DOI: 10.1016/j.aller.2016.09.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 09/05/2016] [Indexed: 01/26/2023]
Abstract
Allergic respiratory diseases are major health problems in paediatric population due their high level of prevalence and chronicity, and to their relevance in the costs and quality of life. One of the most important risk factors for the development of airway diseases in children and adolescents is atopy. The mainstays for the treatment of these diseases are avoiding allergens, controlling symptoms, and preventing them through sustained desensitization by allergen immunotherapy (AIT). AIT is a treatment option that consists in the administration of increasing amounts of allergens to modify the biological response to them, inducing long-term tolerance even after treatment has ended. This treatment approach has shown to decrease symptoms and improve quality of life, becoming cost effective for a large number of patients. In addition, it is considered the only treatment that can influence the natural course of the disease by targeting the cause of the allergic inflammatory response. The aim of this publication is to reflect the advances of AIT in the diagnosis and treatment of allergic respiratory diseases in children and adolescents reviewing articles published since 2000, establishing evidence categories to support the strength of the recommendations based on evidence. The first part of the article covers the prerequisite issues to understand how AIT is effective, such as the correct etiologic and clinical diagnosis of allergic respiratory diseases. Following this, the article outlines the advancements in understanding the mechanisms by which AIT achieve immune tolerance to allergens. Administration routes, treatment regimens, dose and duration, efficacy, safety, and factors associated with adherence are also reviewed. Finally, the article reviews future advances in the research of AIT.
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Affiliation(s)
- M Tortajada-Girbés
- Paediatric Allergology and Pulmonology Unit, Dr. Peset University Hospital, Valencia, Spain; Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain.
| | - M Mesa Del Castillo
- Paediatric Allergology and Neumology Unit, Hospital El Escorial, Madrid, Spain
| | - H Larramona
- Paediatric Allergology and Pulmonology Unit, Department of Paediatrics, University Autonoma of Barcelona, and Corporacio Sanitaria Parc Tauli, Hospital of Sabadell, Barcelona, Spain
| | - J M Lucas
- Pediatric Allergy and Immunology Unit, Virgen Arrixaca Clinic Universitary Hospital, Murcia, Spain
| | - M Álvaro
- Allergy and Clinical Immunology Section, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
| | - A I Tabar
- Servicio de Alergología. Complejo Hospitalario de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), RETIC de Asma, Reacciones adversas y Alérgicas (ARADYAL), Pamplona, Spain
| | - M J Jerez
- Publications Office of the European Union, Luxembourg
| | - A Martínez-Cañavate
- Paediatric Allergology and Neumology Unit, Complejo Hospitalario Universitario de Granada, Spain
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Abstract
One key approach to increase the efficacy and the safety of immunotherapy is the use of adjuvants. However, many of the adjuvants currently in use can cause adverse events, raising concerns regarding their clinical use, and are geared toward productive immune responses but not necessarily tolerogenic responses. Thus, novel adjuvants for immunotherapy are needed and are being developed. Essential is their potential to boost appropriate tolerogenic adaptive immune responses to allergens while limiting side effects. This review provides an overview of adjuvants currently in clinical use or under development and discusses their therapeutic effect in enhancing allergen-induced tolerance.
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Bielinska AU, O'Konek JJ, Janczak KW, Baker JR. Immunomodulation of TH2 biased immunity with mucosal administration of nanoemulsion adjuvant. Vaccine 2016; 34:4017-24. [PMID: 27317451 PMCID: PMC4962973 DOI: 10.1016/j.vaccine.2016.06.043] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 05/31/2016] [Accepted: 06/07/2016] [Indexed: 11/18/2022]
Abstract
TH2-biased immune responses are associated with inadequate protection against some pathogens and with cancer, colitis, asthma and allergy. Since most currently used vaccine adjuvants induce a TH2-biased response, this has led to interest in developing adjuvants capable of activating TH1 immunity and modulating existing TH2 responses. Immunotherapies to shift immune responses from TH2 to TH1 have generally required prolonged immunization protocols and have not induced effective TH1 responses. We have demonstrated that nanoscale emulsions (NE), a novel mucosal adjuvant, induce robust IgA and IgG antibody responses and TH1/TH17 cellular immunity resulting in protection against a variety of respiratory and mucosal infections. Because intranasal (i.n.) delivery of NE adjuvant consistently induces TH1/TH17 biased responses, we hypothesized that NE could be used as a therapeutic vaccine to redirect existing TH2 polarized immunity towards a more balanced TH1/TH2 profile. To test this, a TH2 immune response was established by intramuscular immunization of mice with alum-adjuvanted hepatitis B surface antigen (HBs), followed by a single subsequent i.n. immunization with NE-HBs. These animals exhibited increased TH1 associated immune responses and IL-17, and decreased TH2 cytokines (IL-4 and IL-5) and IgG1. NE immunization induced regulatory T cells and IL-10, and IL-10 was required for the suppression of TH2 immunity. These data demonstrate that NE-based vaccines can modulate existing TH2 immune responses to promote TH1/TH17 immunity and suggest the potential therapeutic use of NE vaccines for diseases associated with TH2 immunity.
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Affiliation(s)
- Anna U Bielinska
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States
| | - Jessica J O'Konek
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109, United States.
| | - Katarzyna W Janczak
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States
| | - James R Baker
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109, United States.
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Tasaniyananda N, Chaisri U, Tungtrongchitr A, Chaicumpa W, Sookrung N. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine. PLoS One 2016; 11:e0150463. [PMID: 26954254 PMCID: PMC4783078 DOI: 10.1371/journal.pone.0150463] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 02/15/2016] [Indexed: 12/19/2022] Open
Abstract
Cats (Felis domesticus) are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen) in comparison with the vaccine made of crude cat hair extract (cCE). BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L)-entrapped native Fel d 1 (L-nFD1), L-cCE), or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions) towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35) and Treg (up-regulation of IL-10 and TGF-β). In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients.
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Affiliation(s)
- Natt Tasaniyananda
- Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Urai Chaisri
- Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Anchalee Tungtrongchitr
- Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Wanpen Chaicumpa
- Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Nitat Sookrung
- Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- * E-mail:
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Passalacqua G, Rogkakou A, Mincarini M, Canonica GW. Allergen immunotherapy in asthma; what is new? Asthma Res Pract 2015; 1:6. [PMID: 27965760 PMCID: PMC4970380 DOI: 10.1186/s40733-015-0006-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 05/27/2015] [Indexed: 12/29/2022] Open
Abstract
The use and role of allergen immunotherapy (AIT) in asthma is still a matter of debate, and no definite recommendation about this is made in guidelines, both for the subcutaneous and sublingual routes. This is essentially due to the fact that most controlled randomised trials were not specifically designed for asthma, and that objective measures of pulmonary function were only occasionally considered. Nonetheless, in many trials, favourable results in asthma (symptoms, medication usage, bronchial reactivity) were consistently reported. There are also several meta analyses in favour of AIT, although their validity is limited by a relevant methodological heterogeneity. In addition to the crude clinical effect, a disease modifying action of AIT (prevention of asthma onset and long-lasting effects) have been reported. The safety is an important aspect to consider in asthma. Fatalities were rare: in Europe no fatality was reported in the last three decades, as in the United States in the last 4 years. Based on previous surveys, and common sense, uncontrolled asthma is still recognized as the most important risk factor for severe adverse events. On the contrary, there is no evidence that AIT can worsen or induce asthma. According to the available evidence, AIT can be safely used as add-on treatment when asthma is associated with rhinitis (a frequent condition), provided that asthma is adequately controlled by pharmacotherapy. AIT cannot be recommended or suggested as single therapy. When asthma is the unique manifestation of respiratory allergy, its use should be evaluated case by case.
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Affiliation(s)
- Giovanni Passalacqua
- Allergy and Respiratory Diseases, IRCCS San Martino Hospital-IST-University of Genoa, Padiglione Maragliano, L.go R.Benzi 10, Genoa, 16133 Italy
| | - Anthi Rogkakou
- Allergy and Respiratory Diseases, IRCCS San Martino Hospital-IST-University of Genoa, Padiglione Maragliano, L.go R.Benzi 10, Genoa, 16133 Italy
| | - Marcello Mincarini
- Allergy and Respiratory Diseases, IRCCS San Martino Hospital-IST-University of Genoa, Padiglione Maragliano, L.go R.Benzi 10, Genoa, 16133 Italy
| | - Giorgio Walter Canonica
- Allergy and Respiratory Diseases, IRCCS San Martino Hospital-IST-University of Genoa, Padiglione Maragliano, L.go R.Benzi 10, Genoa, 16133 Italy
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Mener DJ, Lin SY. Improvement and prevention of asthma with concomitant treatment of allergic rhinitis and allergen-specific therapy. Int Forum Allergy Rhinol 2015; 5 Suppl 1:S45-50. [PMID: 26072703 DOI: 10.1002/alr.21569] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Revised: 05/05/2015] [Accepted: 05/11/2015] [Indexed: 01/29/2023]
Abstract
BACKGROUND Asthma and allergic rhinitis are 2 of the most prevalent chronic medical diseases. Asthma is estimated to affect 8% of adults and 9% of children, with nearly 300 million people affected worldwide. Poorly controlled allergic rhinitis may be associated with worsening asthma symptoms over time. Various treatments have been proposed in the improvement and prevention of asthma in children and adults with allergic symptoms, which have included pharmacotherapy with antihistamines and topical intranasal corticosteroids, as well as allergen-specific immunotherapy. METHODS Articles were selected through PubMed and personal knowledge of the authors based on a comprehensive literature review examining whether treatment of allergic rhinitis improves and/or prevents concomitant symptoms of asthma. The largest and highest-quality studies were included in the literature review. The search selection was not standardized. Articles written in a language other than English were excluded. RESULTS Clinical trials have showed improvement in asthma symptoms with concomitant treatment of allergic rhinitis with antihistamines and topical intranasal corticosteroids, though improvement in objective pulmonary function parameters has not been uniformly demonstrated with antihistamine use alone. There is very strong evidence to suggest that subcutaneous and sublingual immunotherapy may in addition prevent the progression of asthma in high-risk atopic patients by inducing immunological tolerance. CONCLUSION Traditional pharmacotherapy with antihistamines and topical intranasal steroids has been shown to improve allergic rhinitis symptoms with concomitant allergic asthma; however, only allergen-specific immunotherapy offers long-term control in improving asthma symptoms, exacerbations, and likely ultimate prevention in developing asthma.
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Affiliation(s)
- David J Mener
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD
| | - Sandra Y Lin
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD
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Yukselen A, Kendirli SG. Role of immunotherapy in the treatment of allergic asthma. World J Clin Cases 2014; 2:859-865. [PMID: 25516861 PMCID: PMC4266834 DOI: 10.12998/wjcc.v2.i12.859] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 08/27/2014] [Accepted: 10/16/2014] [Indexed: 02/05/2023] Open
Abstract
Allergen-specific immunotherapy (SIT) induces clinical and immunological tolerance as defined by persistence of clinical benefit and associated long-term immunological parameters after cessation of treatment. Although the efficacy of SIT has been shown in terms of reducing symptoms, medication consumption and ameliorating quality of life in both allergic rhinitis and asthma, there has long been some controversies about effectiveness of SIT in the treatment of allergic asthma. The type of allergen, the dose and protocol of immunotherapy, patient selection criteria, the severity and control of asthma, all are significant contributors to the power of efficacy in allergic asthma. The initiation of SIT in allergic asthma should be considered in case of coexisting of other allergic diseases such as allergic rhinitis, unacceptable adverse effects of medications, patient’s preference to avoid long-term pharmacotherapy. Steroid sparing effect of SIT in allergic asthma is also an important benefit particularly in patients who have to use these drugs in high doses for a long-time. Symptomatic asthma is a risk factor for systemic reactions and asthma should be controlled at the time of administration of SIT. Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been found to be effective in patients with allergic asthma. Although the safety profile of SLIT seems to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT may appear better and earlier than SLIT in children with allergic asthma.
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Yukselen A, Kendirli SG. Subcutaneous and sublingual immunotherapy: Where do we stand? World J Immunol 2014; 4:130-140. [DOI: 10.5411/wji.v4.i3.130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Revised: 05/01/2014] [Accepted: 07/14/2014] [Indexed: 02/05/2023] Open
Abstract
Though symptoms of allergic diseases can be reduced by the use of drugs such as corticosteroids, antihistamines or leukotrien antagonists, the only treatment directed to change the natural course of allergic disease is allergen-specific immunotherapy (SIT). Its efficacy can last years after the cessassion of the treatment. SIT brings on regulatory T cells with the capacity to generate interleukin-10 and transforming growth factor-b, restricts activation of mast cells and basophils, and shifts antibody isotype from IgE to the noninflammatory type immunoglobulin G4. Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the two most used ways at the present for applying SIT. These two treatments were demonstrated to be effective on reducing symptoms and medication use, in prevention of new sensitizations and in protecting from progression of rhinitis to asthma. The safety of SLIT appears to be better than SCIT although there have been a few head to head comparisons. In order to overcome compliance problems or possible systemic side effects which may be faced during this long-term treatment, recent investigations have been focused on the implementation of allergens in quite efficacious and safer ways.
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Aryan Z, Compalati E, Comapalati E, Canonica GW, Rezaei N. Allergen-specific immunotherapy in asthmatic children: from the basis to clinical applications. Expert Rev Vaccines 2013; 12:639-59. [PMID: 23750794 DOI: 10.1586/erv.13.45] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Atopic asthma in childhood with the tendency to persist into adult life is an important issue in pediatrics. Allergen-specific immunotherapy (SIT) is the only curative treatment option for these children, being directed to the causes of the disease. The Th2 phenotype is a predominant immunological pattern in atopic asthma and SIT leads to apoptosis/anergy of T cells and induces immune-regulatory responses and immune deviation towards Th1. Many factors can affect the safety and efficacy of SIT, such as pattern of sensitization, allergy vaccine (allergen extracts, adjuvants and conjugated molecules), route of administration (subcutaneous or sublingual) and different treatment schedules. Overall, asthma symptoms and medication scores usually decrease following a SIT course and the most common observed side effects are restricted to local swelling, erythema and pruritus. Compared with conventional pharmacotherapy, SIT may be more cost effective, providing a benefit after discontinuation and a steroid-sparing effect. In addition, it can prevent new sensitizations in monosensitized asthmatic children. Microbial supplements such as probiotics, immunomodulatory substances like anti-IgE/leukotrienes, antibodies and newer allergen preparations such as recombinant forms have been tested to improve the efficacy and safety of SIT with inconclusive results. In conclusion, SIT provides an appropriate solution for childhood asthma that should be employed more often in clinical practice. Further studies are awaited to improve current knowledge regarding the mechanisms behind SIT and determine the most appropriate materials and schedule of immunotherapy for children with asthma.
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Affiliation(s)
- Zahra Aryan
- Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Viswanathan RK, Busse WW. Allergen immunotherapy in allergic respiratory diseases: from mechanisms to meta-analyses. Chest 2012; 141:1303-1314. [PMID: 22553263 DOI: 10.1378/chest.11-2800] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Allergen-specific immunotherapy (SIT) involves the repeated administration of allergenic extracts to atopic individuals over a period of 3 to 5 years either subcutaneously (SCIT) or sublingually (SLIT) for the treatment of allergic respiratory diseases, including asthma and allergic rhinitis (AR). In studies, SCIT and SLIT have been shown to improve existing symptoms of asthma and AR and to also have the capability to cause disease-modifying changes of the underlying atopic condition so as to prevent new allergic sensitization as well as arrest progression of AR to asthma. Recent evidence suggests that immunotherapy brings about these effects through actions that use T-regulatory cells and blocking antibodies such as IgG(4) and IgA(2,) which can then result in an "immune deviation" from a T-helper (Th) 2 cell pattern to a Th1 cell pattern. Numerous meta-analyses and studies have been performed to evaluate the existing data among these studies, with the consensus recommendation favoring the use of immunotherapy because of its potential to modify existing diseases. Significant adverse reactions can occur with immunotherapy, including anaphylaxis and, very rarely, death. A primary factor in considering SIT is its potential to provide long-lasting effects that are able to be sustained well after its discontinuation. Given the significant burden these allergic diseases impose on the health-care system, SIT appears to be a cost-effective adjunctive treatment in modifying the existing disease state.
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Affiliation(s)
- Ravi K Viswanathan
- Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - William W Busse
- Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
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Moutinho CG, Matos CM, Teixeira JA, Balcão VM. Nanocarrier possibilities for functional targeting of bioactive peptides and proteins: state-of-the-art. J Drug Target 2011; 20:114-41. [PMID: 22023555 DOI: 10.3109/1061186x.2011.628397] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This review attempts to provide an updated compilation of studies reported in the literature pertaining to production of nanocarriers encasing peptides and/or proteins, in a way that helps the reader direct a bibliographic search and develop an integrated perspective of the subject. Highlights are given to bioactive proteins and peptides, with a special focus on those from dairy sources (including physicochemical characteristics and properties, and biopharmaceutical application possibilities of e.g. lactoferrin and glycomacropeptide), as well as to nanocarrier functional targeting. Features associated with micro- and (multiple) nanoemulsions, micellar systems, liposomes and solid lipid nanoparticles, together with biopharmaceutical considerations, are presented in the text in a systematic fashion.
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Affiliation(s)
- Carla G Moutinho
- Bioengineering and Biopharmaceutical Chemistry Research Group, Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal
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