{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:41:15Z","timestamp":1793241675822,"version":"4.5.0"},"reference-count":129,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Juvenile Diabetes Research Foundation","award":["3SRA-2017-492-A-N"],"award-info":[{"award-number":["3SRA-2017-492-A-N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5\u2032cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases.<\/jats:p>","DOI":"10.3390\/vaccines12060670","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T11:14:16Z","timestamp":1718622856000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["mRNA Technology and Mucosal Immunization"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-2126","authenticated-orcid":false,"given":"Antonio","family":"Toniolo","sequence":"first","affiliation":[{"name":"Global Virus Network, University of Insubria Medical School, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-3583","authenticated-orcid":false,"given":"Giuseppe","family":"Maccari","sequence":"additional","affiliation":[{"name":"Data Science for Health (DaScH) Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-232X","authenticated-orcid":false,"given":"Giovanni","family":"Camussi","sequence":"additional","affiliation":[{"name":"Department of Medical Science, University of Turin, A.O.U. Citt\u00e0 della Salute e della Scienza di Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA","volume":"23","author":"Buckstein","year":"2005","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1038\/mt.2008.200","article-title":"Incorporation of Pseudouridine Into MRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability","volume":"16","author":"Muramatsu","year":"2008","journal-title":"Mol. 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