{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:02:04Z","timestamp":1777914124259,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Takis Biotech, Rome, Italy"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>COVID-19 is a rapidly spreading disease, posing a huge hazard to global health. The plasmid vaccine pTK1A-TPA-SpikeA (named COVID- eVax) encodes the severe acute respiratory syndrome coronavirus 2 S protein receptor-binding domain, developed for intramuscular injection followed by electroporation (EP). The aim of this study was to assess the systemic toxicity and local tolerance of COVID- eVax delivered intramuscularly followed by EP in Sprague Dawley (SD) rats. The animals were killed 2 days and 4 weeks after the last injection (30-day and 57-day, respectively). No mortality was observed, and no signs of toxicity were evident, including injection site reactions. A lasting and specific immune response was observed in all treated animals, confirming the relevance of the rat as a toxicological model for this vaccine. Histopathological evaluation revealed muscle fiber necrosis associated with subchronic inflammation at the injection sites (at the 30-day time point), with a clear trend for recovery at the 57-day time point, which is expected following EP, and considered a desirable effect to mount the immune response against the target antigen. In conclusion, the intramuscular EP-assisted DNA vaccine, COVID- eVax showed an excellent safety profile in SD rats under these experimental conditions and supports its further development for use in humans.<\/jats:p>","DOI":"10.1177\/01926233211042263","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T04:21:07Z","timestamp":1631074867000},"page":"1255-1268","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Toxicity and Local Tolerance of COVID-\n                    <i>e<\/i>\n                    Vax, a Plasmid DNA Vaccine for SARS-CoV-2, Delivered by Electroporation"],"prefix":"10.1177","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8606-8385","authenticated-orcid":false,"given":"Yuval","family":"Ramot","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Department of Dermatology, Hadassah Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1075-7408","authenticated-orcid":false,"given":"Gianfranco","family":"Caselli","sequence":"additional","affiliation":[{"name":"Rottapharm Biotech S.r.l., Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Aurisicchio","sequence":"additional","affiliation":[{"name":"Takis Biotech, Rome, Italy"},{"name":"Evvivax Biotech, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Andreini","sequence":"additional","affiliation":[{"name":"AKROS BioScience Srl, Pomezia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Marra","sequence":"additional","affiliation":[{"name":"Takis Biotech, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Luberto","sequence":"additional","affiliation":[{"name":"Takis Biotech, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Stoppoloni","sequence":"additional","affiliation":[{"name":"Takis Biotech, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Lucrezia","family":"Pacello","sequence":"additional","affiliation":[{"name":"Takis Biotech, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-796X","authenticated-orcid":false,"given":"Laura","family":"Monetini","sequence":"additional","affiliation":[{"name":"ERBC, Pomezia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Nyska","sequence":"additional","affiliation":[{"name":"Tel Aviv University, Tel-Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"bibr1-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112239"},{"key":"bibr2-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2554-8"},{"key":"bibr3-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268820001235"},{"key":"bibr4-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101765"},{"key":"bibr5-01926233211042263","doi-asserted-by":"publisher","DOI":"10.3390\/v12080861"},{"key":"bibr6-01926233211042263","author":"Conforti A","year":"2021","journal-title":"biorxiv"},{"key":"bibr7-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2013.836903"},{"key":"bibr8-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.06.041"},{"key":"bibr9-01926233211042263","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113605"},{"key":"bibr10-01926233211042263","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01963"},{"key":"bibr11-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1330236"},{"key":"bibr12-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2004.01.015"},{"key":"bibr13-01926233211042263","doi-asserted-by":"publisher","DOI":"10.4161\/onci.28540"},{"key":"bibr14-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2017.105"},{"key":"bibr15-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04547-2"},{"key":"bibr16-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2012.01.002"},{"key":"bibr17-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2012.04.003"},{"key":"bibr18-01926233211042263","doi-asserted-by":"publisher","DOI":"10.1177\/0192623319875085"},{"key":"bibr19-01926233211042263","unstructured":"World Health Organization. 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