Design, production and immunomodulatory potency of a novel allergen bioparticle

Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the ris...

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Veröffentlicht in:PloS one 2020-12, Vol.15 (12), p.e0242867
Hauptverfasser: Gomord, Véronique, Stordeur, Virginie, Fitchette, Anne-Catherine, Fixman, Elizabeth D, Tropper, Guy, Garnier, Lorna, Desgagnes, Réjean, Viel, Sébastien, Couillard, Julie, Beauverger, Guillaume, Trepout, Sylvain, Ward, Brian J, van Ree, Ronald, Faye, Loic, Vézina, Louis-P
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container_issue 12
container_start_page e0242867
container_title PloS one
container_volume 15
creator Gomord, Véronique
Stordeur, Virginie
Fitchette, Anne-Catherine
Fixman, Elizabeth D
Tropper, Guy
Garnier, Lorna
Desgagnes, Réjean
Viel, Sébastien
Couillard, Julie
Beauverger, Guillaume
Trepout, Sylvain
Ward, Brian J
van Ree, Ronald
Faye, Loic
Vézina, Louis-P
description Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. To become a more attractive alternative to lifelong symptomatic drug use, improvements to AIT are needed. Among the most promising new immunotherapy strategies is the use of bioparticles for the presentation of target antigen to the immune system as they can elicit strong T cell and B cell immune responses. Virus-like particles (VLPs) are a specific class of bioparticles in which the structural and immunogenic constituents are from viral origin. However, VLPs are ill-suited for use in AIT as their antigenicity is linked to structure. Recently, synthetic biology has been used to produce artificial modular bioparticles, in which supramolecular assemblies are made of elements from heterogeneous biological sources promoting the design and use of in vivo-assembling enveloped bioparticles for viral and non-viral antigens presentation. We have used a coiled-coil hybrid assembly for the design of an enveloped bioparticle (eBP) that present trimers of the Der p 2 allergen at its surface, This bioparticle was produced as recombinant and in vivo assembled eBPs in plant. This allergen biotherapeutic was used to demonstrate i) the capacity of plants to produce synthetic supramolecular allergen bioparticles, and ii) the immunomodulatory potential of naturally-assembled allergen bioparticles. Our results show that allergens exposed on eBPs induced a very strong IgG response consisting predominantly of IgG2a in favor of the TH1 response. Finally, our results demonstrate that rDer p 2 present on the surface of BPs show a very limited potential to stimulate the basophil degranulation of patient allergic to this allergen which is predictive of a high safety potential.
doi_str_mv 10.1371/journal.pone.0242867
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Recently, synthetic biology has been used to produce artificial modular bioparticles, in which supramolecular assemblies are made of elements from heterogeneous biological sources promoting the design and use of in vivo-assembling enveloped bioparticles for viral and non-viral antigens presentation. We have used a coiled-coil hybrid assembly for the design of an enveloped bioparticle (eBP) that present trimers of the Der p 2 allergen at its surface, This bioparticle was produced as recombinant and in vivo assembled eBPs in plant. This allergen biotherapeutic was used to demonstrate i) the capacity of plants to produce synthetic supramolecular allergen bioparticles, and ii) the immunomodulatory potential of naturally-assembled allergen bioparticles. Our results show that allergens exposed on eBPs induced a very strong IgG response consisting predominantly of IgG2a in favor of the TH1 response. 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However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. To become a more attractive alternative to lifelong symptomatic drug use, improvements to AIT are needed. Among the most promising new immunotherapy strategies is the use of bioparticles for the presentation of target antigen to the immune system as they can elicit strong T cell and B cell immune responses. Virus-like particles (VLPs) are a specific class of bioparticles in which the structural and immunogenic constituents are from viral origin. However, VLPs are ill-suited for use in AIT as their antigenicity is linked to structure. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gomord, Véronique</au><au>Stordeur, Virginie</au><au>Fitchette, Anne-Catherine</au><au>Fixman, Elizabeth D</au><au>Tropper, Guy</au><au>Garnier, Lorna</au><au>Desgagnes, Réjean</au><au>Viel, Sébastien</au><au>Couillard, Julie</au><au>Beauverger, Guillaume</au><au>Trepout, Sylvain</au><au>Ward, Brian J</au><au>van Ree, Ronald</au><au>Faye, Loic</au><au>Vézina, Louis-P</au><au>Chapoval, Svetlana P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, production and immunomodulatory potency of a novel allergen bioparticle</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>15</volume><issue>12</issue><spage>e0242867</spage><pages>e0242867-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. To become a more attractive alternative to lifelong symptomatic drug use, improvements to AIT are needed. Among the most promising new immunotherapy strategies is the use of bioparticles for the presentation of target antigen to the immune system as they can elicit strong T cell and B cell immune responses. Virus-like particles (VLPs) are a specific class of bioparticles in which the structural and immunogenic constituents are from viral origin. However, VLPs are ill-suited for use in AIT as their antigenicity is linked to structure. Recently, synthetic biology has been used to produce artificial modular bioparticles, in which supramolecular assemblies are made of elements from heterogeneous biological sources promoting the design and use of in vivo-assembling enveloped bioparticles for viral and non-viral antigens presentation. We have used a coiled-coil hybrid assembly for the design of an enveloped bioparticle (eBP) that present trimers of the Der p 2 allergen at its surface, This bioparticle was produced as recombinant and in vivo assembled eBPs in plant. This allergen biotherapeutic was used to demonstrate i) the capacity of plants to produce synthetic supramolecular allergen bioparticles, and ii) the immunomodulatory potential of naturally-assembled allergen bioparticles. Our results show that allergens exposed on eBPs induced a very strong IgG response consisting predominantly of IgG2a in favor of the TH1 response. Finally, our results demonstrate that rDer p 2 present on the surface of BPs show a very limited potential to stimulate the basophil degranulation of patient allergic to this allergen which is predictive of a high safety potential.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33259521</pmid><doi>10.1371/journal.pone.0242867</doi><tpages>e0242867</tpages><orcidid>https://orcid.org/0000-0003-4884-9874</orcidid><orcidid>https://orcid.org/0000-0001-7062-9136</orcidid><orcidid>https://orcid.org/0000-0002-5085-443X</orcidid><orcidid>https://orcid.org/0000-0002-5822-407X</orcidid><oa>free_for_read</oa></addata></record>
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1932-6203
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source MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects Allergens
Allergens - biosynthesis
Allergens - chemistry
Allergens - immunology
Allergy
Aluminum
Amino Acid Sequence
Animals
Antigen presentation
Antigenicity
Antigens
Antigens, Dermatophagoides - immunology
Assembling
Basophils - immunology
Biological products
Biology and Life Sciences
Bronchial Hyperreactivity - immunology
Bronchoalveolar Lavage Fluid
Care and treatment
Degranulation
Design
DNA - metabolism
Female
Food allergies
Human papillomavirus
Humans
Hypersensitivity - immunology
Immune response (cell-mediated)
Immune system
Immunization
Immunogenicity
Immunoglobulin G
Immunomodulation
Immunomodulation - immunology
Immunosuppressive agents
Immunotherapy
Influenza
Lymphocytes
Lymphocytes T
Medical treatment
Medicine and Health Sciences
Methods
Mice, Inbred BALB C
Modular structures
Nanoparticles - chemistry
Nanoparticles - ultrastructure
People and Places
Peptides
Production processes
Protein Processing, Post-Translational
Proteins
Recombinant Proteins - biosynthesis
Recombinant Proteins - chemistry
Side effects
Synthetic biology
Synthetic products
Trimers
Vaccines
Virus-like particles
Viruses
title Design, production and immunomodulatory potency of a novel allergen bioparticle
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