Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers
mRNA-based vaccines were effective in contrasting SARS-CoV-2 infection. However, they presented several limitations of storage and supply chain, and their parenteral administration elicited a limited mucosal IgA immune response. Extracellular vesicles (EVs) have been recognized as a mechanism of cel...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/14/1826 |
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| author | Margherita A. C. Pomatto Chiara Gai Federica Negro Lucia Massari Maria Chiara Deregibus Francesco Giuseppe De Rosa Giovanni Camussi |
| author_facet | Margherita A. C. Pomatto Chiara Gai Federica Negro Lucia Massari Maria Chiara Deregibus Francesco Giuseppe De Rosa Giovanni Camussi |
| author_sort | Margherita A. C. Pomatto |
| collection | DOAJ |
| description | mRNA-based vaccines were effective in contrasting SARS-CoV-2 infection. However, they presented several limitations of storage and supply chain, and their parenteral administration elicited a limited mucosal IgA immune response. Extracellular vesicles (EVs) have been recognized as a mechanism of cell-to-cell communication well-preserved in all life kingdoms, including plants. Their membrane confers protection from enzyme degradation to encapsulated nucleic acids favoring their transfer between cells. In the present study, EVs derived from the juice of an edible plant (<i>Citrus sinensis</i>) (oEVs) were investigated as carriers of an orally administered mRNA vaccine coding for the S1 protein subunit of SARS-CoV-2 with gastro-resistant oral capsule formulation. The mRNA loaded into oEVs was protected and was stable at room temperature for one year after lyophilization and encapsulation. Rats immunized via gavage administration developed a humoral immune response with the production of specific IgM, IgG, and IgA, which represent the first mucosal barrier in the adaptive immune response. The vaccination also triggered the generation of blocking antibodies and specific lymphocyte activation. In conclusion, the formulation of lyophilized mRNA-containing oEVs represents an efficient delivery strategy for oral vaccines due to their stability at room temperature, optimal mucosal absorption, and the ability to trigger an immune response. |
| first_indexed | 2024-03-11T01:12:57Z |
| format | Article |
| id | doaj.art-b9e61cd2048a4ddb848af6d03e02e60b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:12:57Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b9e61cd2048a4ddb848af6d03e02e60b2023-11-18T18:45:42ZengMDPI AGCells2073-44092023-07-011214182610.3390/cells12141826Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle CarriersMargherita A. C. Pomatto0Chiara Gai1Federica Negro2Lucia Massari3Maria Chiara Deregibus4Francesco Giuseppe De Rosa5Giovanni Camussi6EvoBiotech s.r.l., 10122 Turin, ItalyEvoBiotech s.r.l., 10122 Turin, ItalyEvoBiotech s.r.l., 10122 Turin, ItalyEvoBiotech s.r.l., 10122 Turin, ItalyDepartment of Medical Science, University of Turin, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, ItalyDepartment of Medical Science, University of Turin, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, ItalyEvoBiotech s.r.l., 10122 Turin, ItalymRNA-based vaccines were effective in contrasting SARS-CoV-2 infection. However, they presented several limitations of storage and supply chain, and their parenteral administration elicited a limited mucosal IgA immune response. Extracellular vesicles (EVs) have been recognized as a mechanism of cell-to-cell communication well-preserved in all life kingdoms, including plants. Their membrane confers protection from enzyme degradation to encapsulated nucleic acids favoring their transfer between cells. In the present study, EVs derived from the juice of an edible plant (<i>Citrus sinensis</i>) (oEVs) were investigated as carriers of an orally administered mRNA vaccine coding for the S1 protein subunit of SARS-CoV-2 with gastro-resistant oral capsule formulation. The mRNA loaded into oEVs was protected and was stable at room temperature for one year after lyophilization and encapsulation. Rats immunized via gavage administration developed a humoral immune response with the production of specific IgM, IgG, and IgA, which represent the first mucosal barrier in the adaptive immune response. The vaccination also triggered the generation of blocking antibodies and specific lymphocyte activation. In conclusion, the formulation of lyophilized mRNA-containing oEVs represents an efficient delivery strategy for oral vaccines due to their stability at room temperature, optimal mucosal absorption, and the ability to trigger an immune response.https://www.mdpi.com/2073-4409/12/14/1826oralcapsuleextracellular vesiclesplantdeliverycarrier |
| spellingShingle | Margherita A. C. Pomatto Chiara Gai Federica Negro Lucia Massari Maria Chiara Deregibus Francesco Giuseppe De Rosa Giovanni Camussi Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers Cells oral capsule extracellular vesicles plant delivery carrier |
| title | Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers |
| title_full | Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers |
| title_fullStr | Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers |
| title_full_unstemmed | Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers |
| title_short | Oral Delivery of mRNA Vaccine by Plant-Derived Extracellular Vesicle Carriers |
| title_sort | oral delivery of mrna vaccine by plant derived extracellular vesicle carriers |
| topic | oral capsule extracellular vesicles plant delivery carrier |
| url | https://www.mdpi.com/2073-4409/12/14/1826 |
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