Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines
Virus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived fro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.986823/full |
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| author | Diego Pazos-Castro Diego Pazos-Castro Clémence Margain Zulema Gonzalez-Klein Zulema Gonzalez-Klein Marina Amores-Borge Marina Amores-Borge Carmen Yuste-Calvo Maria Garrido-Arandia Maria Garrido-Arandia Lucía Zurita Vanesa Esteban Jaime Tome-Amat Araceli Diaz-Perales Araceli Diaz-Perales Fernando Ponz |
| author_facet | Diego Pazos-Castro Diego Pazos-Castro Clémence Margain Zulema Gonzalez-Klein Zulema Gonzalez-Klein Marina Amores-Borge Marina Amores-Borge Carmen Yuste-Calvo Maria Garrido-Arandia Maria Garrido-Arandia Lucía Zurita Vanesa Esteban Jaime Tome-Amat Araceli Diaz-Perales Araceli Diaz-Perales Fernando Ponz |
| author_sort | Diego Pazos-Castro |
| collection | DOAJ |
| description | Virus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived from Turnip mosaic virus (TuMV) have proven to present a tridimensional structure suited to display molecules of interest on their surface, making them interesting tools to be studied in theragnostic strategies. Here, we study their potential in the treatment of food allergy by genetically coupling TuMV-derived VLPs to Pru p 3, one of the most dominant allergens in Mediterranean climates. VLPs-Pru p 3 were generated by cloning a synthetic gene encoding the TuMV coat protein and Pru p 3, separated by a linker, into a transient high-expression vector, followed by agroinfiltration in Nicotiana benthamiana plants. The generated fusion protein self-assembled in planta to form the VLPs, which were purified by exclusion chromatography. Their elongated morphology was confirmed by electron microscopy and their size (~400 nm), and monodispersity was confirmed by dynamic light scattering. Initial in vitro characterization confirmed that they were able to induce proliferation of human immune cells. This proliferative capability was enhanced when coupled with the natural lipid ligand of Pru p 3. The resultant formulation, called VLP-Complex, was also able to be transported by intestinal epithelial cells, without affecting the monolayer integrity. In light of all these results, VLP-Complex was furtherly tested in a mouse model of food allergy. Sublingual administration of VLP-Complex could effectively reduce some serological markers associated with allergic responses in mice, such as anti-Pru p 3 sIgE and sIgG2a. Noteworthy, no associated macroscopic, nephritic, or hepatic toxicity was detected, as assessed by weight, blood urea nitrogen (BUN) and galectin-3 analyses, respectively. Our results highlight the standardized production of allergen-coated TuMV-VLPs in N. benthamiana plants. The resulting formula exerts notable immunomodulatory properties without the need for potentially hazardous adjuvants. Accordingly, no detectable toxicity associated to their administration was detected. As a result, we propose them as good candidates to be furtherly studied in the treatment of immune-based pathologies. |
| first_indexed | 2024-04-10T21:28:42Z |
| format | Article |
| id | doaj.art-aa97e47960594f7d835f3f0b28740ca0 |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T21:28:42Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aa97e47960594f7d835f3f0b28740ca02023-01-19T15:09:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.986823986823Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccinesDiego Pazos-Castro0Diego Pazos-Castro1Clémence Margain2Zulema Gonzalez-Klein3Zulema Gonzalez-Klein4Marina Amores-Borge5Marina Amores-Borge6Carmen Yuste-Calvo7Maria Garrido-Arandia8Maria Garrido-Arandia9Lucía Zurita10Vanesa Esteban11Jaime Tome-Amat12Araceli Diaz-Perales13Araceli Diaz-Perales14Fernando Ponz15Centre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Allergy and Immunology, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainDepartment of Biotechnology-Plant Biology, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas (ETSIAAB), Universidad Politécnica de Madrid, Madrid, SpainCentre for Plant Biotechnology and Genomics, Universidad Politécnica de Madrid – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria / Consejo Superior de Investigaciones Científicas (UPM–INIA/CSIC), Universidad Politécnica de Madrid, Madrid, SpainVirus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived from Turnip mosaic virus (TuMV) have proven to present a tridimensional structure suited to display molecules of interest on their surface, making them interesting tools to be studied in theragnostic strategies. Here, we study their potential in the treatment of food allergy by genetically coupling TuMV-derived VLPs to Pru p 3, one of the most dominant allergens in Mediterranean climates. VLPs-Pru p 3 were generated by cloning a synthetic gene encoding the TuMV coat protein and Pru p 3, separated by a linker, into a transient high-expression vector, followed by agroinfiltration in Nicotiana benthamiana plants. The generated fusion protein self-assembled in planta to form the VLPs, which were purified by exclusion chromatography. Their elongated morphology was confirmed by electron microscopy and their size (~400 nm), and monodispersity was confirmed by dynamic light scattering. Initial in vitro characterization confirmed that they were able to induce proliferation of human immune cells. This proliferative capability was enhanced when coupled with the natural lipid ligand of Pru p 3. The resultant formulation, called VLP-Complex, was also able to be transported by intestinal epithelial cells, without affecting the monolayer integrity. In light of all these results, VLP-Complex was furtherly tested in a mouse model of food allergy. Sublingual administration of VLP-Complex could effectively reduce some serological markers associated with allergic responses in mice, such as anti-Pru p 3 sIgE and sIgG2a. Noteworthy, no associated macroscopic, nephritic, or hepatic toxicity was detected, as assessed by weight, blood urea nitrogen (BUN) and galectin-3 analyses, respectively. Our results highlight the standardized production of allergen-coated TuMV-VLPs in N. benthamiana plants. The resulting formula exerts notable immunomodulatory properties without the need for potentially hazardous adjuvants. Accordingly, no detectable toxicity associated to their administration was detected. As a result, we propose them as good candidates to be furtherly studied in the treatment of immune-based pathologies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.986823/fullvirus-like particlesantigen deliveryfood allergyimmunotherapyplant biotechnologyturnip mosaic virus |
| spellingShingle | Diego Pazos-Castro Diego Pazos-Castro Clémence Margain Zulema Gonzalez-Klein Zulema Gonzalez-Klein Marina Amores-Borge Marina Amores-Borge Carmen Yuste-Calvo Maria Garrido-Arandia Maria Garrido-Arandia Lucía Zurita Vanesa Esteban Jaime Tome-Amat Araceli Diaz-Perales Araceli Diaz-Perales Fernando Ponz Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines Frontiers in Immunology virus-like particles antigen delivery food allergy immunotherapy plant biotechnology turnip mosaic virus |
| title | Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines |
| title_full | Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines |
| title_fullStr | Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines |
| title_full_unstemmed | Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines |
| title_short | Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines |
| title_sort | suitability of potyviral recombinant virus like particles bearing a complete food allergen for immunotherapy vaccines |
| topic | virus-like particles antigen delivery food allergy immunotherapy plant biotechnology turnip mosaic virus |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.986823/full |
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