{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:31:14Z","timestamp":1790983874449,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001340","name":"W. W. Smith Charitable Trust","doi-asserted-by":"publisher","award":["68112\u201001\u2010383"],"award-info":[{"award-number":["68112\u201001\u2010383"]}],"id":[{"id":"10.13039\/100001340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"Norges Idrettsh\u00f8gskole","doi-asserted-by":"publisher","award":["R01GM103899"],"award-info":[{"award-number":["R01GM103899"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"Norges Idrettsh\u00f8gskole","doi-asserted-by":"publisher","award":["R01GM129357"],"award-info":[{"award-number":["R01GM129357"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nanotechnologies are considered to be of growing importance to the vaccine field. Through decoration of immunogens on multivalent nanoparticles, designed nanovaccines can elicit improved humoral immunity. However, significant practical and monetary challenges in large\u2010scale production of nanovaccines have impeded their widespread clinical translation. Here, an alternative approach is illustrated integrating computational protein modeling and adaptive electroporation\u2010mediated synthetic DNA delivery, thus enabling direct in vivo production of nanovaccines. DNA\u2010launched nanoparticles are demonstrated displaying an HIV immunogen spontaneously self\u2010assembled in vivo. DNA\u2010launched nanovaccines induce stronger humoral responses than their monomeric counterparts in both mice and guinea pigs, and uniquely elicit CD8+ effector T\u2010cell immunity as compared to recombinant protein nanovaccines. Improvements in vaccine responses recapitulate when DNA\u2010launched nanovaccines with alternative scaffolds and decorated antigen are designed and evaluated. Finally, evaluation of functional immune responses induced by DLnanovaccines demonstrates that, in comparison to control mice or mice immunized with DNA\u2010encoded hemagglutinin monomer, mice immunized with a DNA\u2010launched hemagglutinin nanoparticle vaccine fully survive a lethal influenza challenge, and have substantially lower viral load, weight loss, and influenza\u2010induced lung pathology. Additional study of these next\u2010generation in vivo\u2010produced nanovaccines may offer advantages for immunization against multiple disease targets.<\/jats:p>","DOI":"10.1002\/advs.201902802","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T03:21:09Z","timestamp":1582773669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure\u2010Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity"],"prefix":"10.1002","volume":"7","author":[{"given":"Ziyang","family":"Xu","sequence":"first","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"},{"name":"Department of Pharmacology Perelman School of Medicine University of Pennsylvania  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Wise","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Plymouth Meeting  Philadelphia PA 19422 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neethu","family":"Chokkalingam","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Walker","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Tello\u2010Ruiz","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah T. C.","family":"Elliott","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Perales\u2010Puchalt","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhou","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth A.","family":"Pumroy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Perelman School of Medicine University of Pennsylvania  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Plymouth Meeting  Philadelphia PA 19422 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Schultheis","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Plymouth Meeting  Philadelphia PA 19422 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Schade","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Plymouth Meeting  Philadelphia PA 19422 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Menis","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology The Scripps Research Institute  La Jolla CA 92037 USA"},{"name":"IAVI Neutralizing Antibody Center The Scripps Research Institute  La Jolla CA 92037 USA"},{"name":"Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery The Scripps Research Institute  La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Guzman","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Andersen","sequence":"additional","affiliation":[{"name":"Bioqual  Rockville MD 20852 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate E.","family":"Broderick","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Plymouth Meeting  Philadelphia PA 19422 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent M.","family":"Humeau","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Plymouth Meeting  Philadelphia PA 19422 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar","family":"Muthumani","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Moiseenkova\u2010Bell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Perelman School of Medicine University of Pennsylvania  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Schief","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology The Scripps Research Institute  La Jolla CA 92037 USA"},{"name":"IAVI Neutralizing Antibody Center The Scripps Research Institute  La Jolla CA 92037 USA"},{"name":"Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery The Scripps Research Institute  La Jolla CA 92037 USA"},{"name":"Ragon Institute of MGH MIT and Harvard  Cambridge MA 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Weiner","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0527-3804","authenticated-orcid":false,"given":"Daniel W.","family":"Kulp","sequence":"additional","affiliation":[{"name":"The Vaccine and Immunotherapy Center The Wistar Institute  Philadelphia PA 19104 USA"},{"name":"Department of Microbiology Perelman School of Medicine University of Pennsylvania  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1002842"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10040167"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400472111"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00239-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00013"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.11.069"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198010093031501"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.04.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1088\/0957-4484\/24\/29\/295102"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/am2013008"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.12.157"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2017.07.010"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.12.001"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2019.03.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.046"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-015-0210-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/ntno.19796"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9339-4"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-1945-9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25159"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01181-17"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2011.07.009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-052-2_21"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-121217-094234"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9120"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac5894"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah3945"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9195"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai9137"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.9.4040-4047.2001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.9.4156"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.03.008"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.08.027"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.10.016"},{"key":"e_1_2_9_36_1","author":"Wise M. C.","year":"2019","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_37_1","author":"Tebas P.","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz132"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit236"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30266-X"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02780"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29131"},{"key":"e_1_2_9_43_1","unstructured":"A Phase I Trial to Evaluate the Safety and Immunogenicity of eOD\u2010GT8 60mer Vaccine Adjuvanted.https:\/\/ClinicalTrials.gov\/show\/NCT03547245."},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah6157"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11826"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25982"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofv067"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0305-x"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2432"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.7.2.175"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113605"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12202"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122659"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040111"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.010"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00272"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2016.01.016"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0320-6"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00014"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/89289"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/79470"},{"key":"e_1_2_9_62_1","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.4049\/jimmunol.160.12.5707","volume":"160","author":"Chattergoon M. A.","year":"1998","journal-title":"J. Immunol."},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.1.169"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.09.086"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1433516"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.24679"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.22968"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.005"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.11.010"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fadvs.201902802","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.201902802","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.201902802","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.201902802","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T20:11:46Z","timestamp":1759781506000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.201902802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,27]]},"references-count":69,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/advs.201902802"],"URL":"https:\/\/doi.org\/10.1002\/advs.201902802","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,27]]},"assertion":[{"value":"2019-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1902802"}}