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In the present study, we evaluated the ability of a family of linear polyethylenimine (PEI<\/jats:styled-content>) polymers, complexed to plasmid DNA<\/jats:styled-content>, to augment DNA<\/jats:styled-content> expression in vivo and to enhance antigen\u2010specific adaptive immune responses. We showed that four of five structurally different PEI<\/jats:styled-content>s that we evaluated increased in vivo DNA<\/jats:styled-content> expression 20\u2010 to 400\u2010fold, and enhanced DNA<\/jats:styled-content>\u2010induced epitope\u2010specific CD<\/jats:styled-content>8+ T<\/jats:styled-content>\u2010cell responses 10\u2010 to 25\u2010fold in BALB<\/jats:styled-content>\/c and C<\/jats:styled-content>57BL<\/jats:styled-content>\/6J<\/jats:styled-content> mice respectively, when delivered intravenously. Functional studies of the PEI<\/jats:styled-content>\u2010DNA<\/jats:styled-content>\u2010induced CD<\/jats:styled-content>8+ T<\/jats:styled-content>\u2010cell responses demonstrated that formulation of DNA<\/jats:styled-content> with PEI<\/jats:styled-content> was associated with increased numbers of cells secreting type I cytokines. In addition, PEI<\/jats:styled-content>\u2010DNA<\/jats:styled-content> complexes improved antigen\u2010specific T<\/jats:styled-content>H<\/jats:sub>1\u2010helper cell and humoral responses. Most importantly, the PEI<\/jats:styled-content>\u2010DNA<\/jats:styled-content> complexes elicited memory cellular responses, capable of rapid expansion and accelerated clearance of a lethal dose of recombinant Listeria monocytogenes<\/jats:italic>. Lastly, we identified physical properties of PEI<\/jats:styled-content>\u2010DNA<\/jats:styled-content> complexes that are associated with enhanced DNA<\/jats:styled-content>\u2010elicited immunogenicity. These findings demonstrate that PEI<\/jats:styled-content> polymers can play an important role in the development of DNA<\/jats:styled-content>\u2010based vaccines in the setting of infectious disease prevention and cancer therapy.<\/jats:p>","DOI":"10.1002\/eji.201242410","type":"journal-article","created":{"date-parts":[[2012,8,7]],"date-time":"2012-08-07T13:49:27Z","timestamp":1344347367000},"page":"2937-2948","source":"Crossref","is-referenced-by-count":31,"title":["Enhancement of plasmid DNA<\/scp> immunogenicity with linear polyethylenimine"],"prefix":"10.1002","volume":"42","author":[{"given":"Evita V.","family":"Grant","sequence":"first","affiliation":[{"name":"Division of Viral Pathogenesis Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mini","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Chemistry Purdue University West Lafayette Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Fortune","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Division of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Klibanov","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Division of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman L.","family":"Letvin","sequence":"additional","affiliation":[{"name":"Division of Viral Pathogenesis Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.COH.0000232346.08285.a8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(05)55002-8"},{"key":"e_1_2_6_4_1","first-page":"201","article-title":"Overview of recent DNA vaccine development for fish","volume":"121","author":"Kurath G.","year":"2005","journal-title":"Dev. 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