Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model
There is growing concern about the toxicity of colloidal aluminum salts used as adjuvants in subcutaneous allergen immunotherapy (SCIT). Therefore, alternative adjuvants and delivery systems are being explored to replace alum in SCIT. We applied micellar elastin-like polypeptides (ELPs), a type of s...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1006776/full |
| _version_ | 1811229390943551488 |
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| author | Jolinde van Strien Hans Warmenhoven Hans Warmenhoven Adrian Logiantara Max Makurat Lorenz Aglas Athanasios Bethanis Romain Leboux Leonie van Rijt J. Andrew MacKay Johannes W. van Schijndel Gregory Schneider René Olsthoorn Wim Jiskoot Ronald van Ree Ronald van Ree Alexander Kros |
| author_facet | Jolinde van Strien Hans Warmenhoven Hans Warmenhoven Adrian Logiantara Max Makurat Lorenz Aglas Athanasios Bethanis Romain Leboux Leonie van Rijt J. Andrew MacKay Johannes W. van Schijndel Gregory Schneider René Olsthoorn Wim Jiskoot Ronald van Ree Ronald van Ree Alexander Kros |
| author_sort | Jolinde van Strien |
| collection | DOAJ |
| description | There is growing concern about the toxicity of colloidal aluminum salts used as adjuvants in subcutaneous allergen immunotherapy (SCIT). Therefore, alternative adjuvants and delivery systems are being explored to replace alum in SCIT. We applied micellar elastin-like polypeptides (ELPs), a type of self-assembling protein, to replace alum as vaccine adjuvant in birch pollen SCIT. ELP and an ELP-Bet v 1 fusion protein were expressed in E. coli and purified by immuno-affinity chromatography and inverse-transition cycling (ITC). Nanoparticles self-assembled from ELP and a 9:1 ELP/ELP-Bet v 1 mixture were characterized by using dynamic light scattering and atomic force microscopy. Allergenicity was assessed by measuring mediator release from rat basophilic leukemia cells transformed with the human FcϵR1 and sensitized with sera derived from human birch pollen allergic patients. Humoral and T-cell immunity were investigated by immunizing naïve mice with the ELP/ELP-Bet v 1 nanoparticles or alum-adsorbed Bet v 1, both containing 36 µg Bet v 1. ELP and ELP/ELP-Bet v 1 self-assembled at 37°C into spherically shaped micelles with a diameter of ~45 nm. ELP conjugation made Bet v 1 hypo-allergenic (10-fold). Compared to alum-adsorbed Bet v 1, ELP/ELP-Bet v 1 nanoparticles induced stronger IgG responses with an earlier onset. Additionally, ELP/ELP-Bet v 1 did not induce Th2 skewing cytokines and IgE. The hypoallergenic character and strong humoral immune response in the absence of a Th2-skewing T-cell response make ELP-based nanoparticles a promising candidate to replace alum in SCIT. |
| first_indexed | 2024-04-12T10:15:20Z |
| format | Article |
| id | doaj.art-ee4f7a6d5ac74d13b0074cd0865161f4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T10:15:20Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ee4f7a6d5ac74d13b0074cd0865161f42022-12-22T03:37:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10067761006776Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity modelJolinde van Strien0Hans Warmenhoven1Hans Warmenhoven2Adrian Logiantara3Max Makurat4Lorenz Aglas5Athanasios Bethanis6Romain Leboux7Leonie van Rijt8J. Andrew MacKay9Johannes W. van Schijndel10Gregory Schneider11René Olsthoorn12Wim Jiskoot13Ronald van Ree14Ronald van Ree15Alexander Kros16Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, NetherlandsDepartment of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam, NetherlandsR&D Department, Haarlems Allergenen Laboratorium (HAL) Allergy B.V., Leiden, NetherlandsDepartment of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, NetherlandsDivision of Allergy and Immunology, Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, AustriaDivision of Allergy and Immunology, Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, AustriaDepartment of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, NetherlandsDepartment of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, United StatesR&D Department, Haarlems Allergenen Laboratorium (HAL) Allergy B.V., Leiden, NetherlandsDepartment of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, NetherlandsDepartment of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, NetherlandsDepartment of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, NetherlandsDepartment of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Otorhinolaryngology, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, NetherlandsThere is growing concern about the toxicity of colloidal aluminum salts used as adjuvants in subcutaneous allergen immunotherapy (SCIT). Therefore, alternative adjuvants and delivery systems are being explored to replace alum in SCIT. We applied micellar elastin-like polypeptides (ELPs), a type of self-assembling protein, to replace alum as vaccine adjuvant in birch pollen SCIT. ELP and an ELP-Bet v 1 fusion protein were expressed in E. coli and purified by immuno-affinity chromatography and inverse-transition cycling (ITC). Nanoparticles self-assembled from ELP and a 9:1 ELP/ELP-Bet v 1 mixture were characterized by using dynamic light scattering and atomic force microscopy. Allergenicity was assessed by measuring mediator release from rat basophilic leukemia cells transformed with the human FcϵR1 and sensitized with sera derived from human birch pollen allergic patients. Humoral and T-cell immunity were investigated by immunizing naïve mice with the ELP/ELP-Bet v 1 nanoparticles or alum-adsorbed Bet v 1, both containing 36 µg Bet v 1. ELP and ELP/ELP-Bet v 1 self-assembled at 37°C into spherically shaped micelles with a diameter of ~45 nm. ELP conjugation made Bet v 1 hypo-allergenic (10-fold). Compared to alum-adsorbed Bet v 1, ELP/ELP-Bet v 1 nanoparticles induced stronger IgG responses with an earlier onset. Additionally, ELP/ELP-Bet v 1 did not induce Th2 skewing cytokines and IgE. The hypoallergenic character and strong humoral immune response in the absence of a Th2-skewing T-cell response make ELP-based nanoparticles a promising candidate to replace alum in SCIT.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1006776/fullBet v 1nanoparticlesaluminumhypo-allergenicelastin-like polypeptidemouse model |
| spellingShingle | Jolinde van Strien Hans Warmenhoven Hans Warmenhoven Adrian Logiantara Max Makurat Lorenz Aglas Athanasios Bethanis Romain Leboux Leonie van Rijt J. Andrew MacKay Johannes W. van Schijndel Gregory Schneider René Olsthoorn Wim Jiskoot Ronald van Ree Ronald van Ree Alexander Kros Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model Frontiers in Immunology Bet v 1 nanoparticles aluminum hypo-allergenic elastin-like polypeptide mouse model |
| title | Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model |
| title_full | Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model |
| title_fullStr | Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model |
| title_full_unstemmed | Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model |
| title_short | Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model |
| title_sort | bet v 1 displaying elastin like polypeptide nanoparticles induce a strong humoral and weak cd4 t cell response against bet v 1 in a murine immunogenicity model |
| topic | Bet v 1 nanoparticles aluminum hypo-allergenic elastin-like polypeptide mouse model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1006776/full |
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