{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:46:04Z","timestamp":1791333964228,"version":"4.3.1"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>DNA vaccines have inherent advantages compared to other vaccine types, including safety, rapid design and construction, ease and speed to manufacture, and thermostability. However, a major drawback of candidate DNA vaccines delivered by needle and syringe is the poor immunogenicity associated with inefficient cellular uptake of the DNA. This uptake is essential because the target vaccine antigen is produced within cells and then presented to the immune system. Multiple techniques have been employed to boost the immunogenicity and protective efficacy of DNA vaccines, including physical delivery methods, molecular and traditional adjuvants, and genetic sequence enhancements. Needle-free injection systems (NFIS) are an attractive alternative due to the induction of potent immunogenicity, enhanced protective efficacy, and elimination of needles. These advantages led to a milestone achievement in the field with the approval for Restricted Use in Emergency Situation of a DNA vaccine against COVID-19, delivered exclusively with NFIS. In this review, we discuss physical delivery methods for DNA vaccines with an emphasis on commercially available NFIS and their resulting safety, immunogenic effectiveness, and protective efficacy. As is discussed, prophylactic DNA vaccines delivered by NFIS tend to induce non-inferior immunogenicity to electroporation and enhanced responses compared to needle and syringe.<\/jats:p>","DOI":"10.3390\/vaccines11020280","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T05:57:23Z","timestamp":1675058243000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Improved DNA Vaccine Delivery with Needle-Free Injection Systems"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-6214","authenticated-orcid":false,"given":"Carmen","family":"Ledesma-Feliciano","sequence":"first","affiliation":[{"name":"PharmaJet, 400 Corporate Circle, Unit N, Golden, CO 80401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9162-2099","authenticated-orcid":false,"given":"Ros","family":"Chapman","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4475-0415","authenticated-orcid":false,"given":"Jay W.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Molecular Virology Branch, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Elma","sequence":"additional","affiliation":[{"name":"PharmaJet, 400 Corporate Circle, Unit N, Golden, CO 80401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin","family":"Zehrung","sequence":"additional","affiliation":[{"name":"PharmaJet, 400 Corporate Circle, Unit N, Golden, CO 80401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles B.","family":"Brennan","sequence":"additional","affiliation":[{"name":"ZabBio, Inc., 11760 Sorrento Valley Road, San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-8758","authenticated-orcid":false,"given":"Erin K.","family":"Spiegel","sequence":"additional","affiliation":[{"name":"PharmaJet, 400 Corporate Circle, Unit N, Golden, CO 80401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2217\/fvl-2021-0170","article-title":"A brief review on DNA vaccines in the era of COVID-19","volume":"17","author":"Shafaati","year":"2022","journal-title":"Future Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1016\/j.drudis.2021.06.008","article-title":"Methods to improve the immunogenicity of plasmid DNA vaccines","volume":"26","author":"Eusebio","year":"2021","journal-title":"Drug Discov. 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