{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:09:15Z","timestamp":1779152955920,"version":"3.51.4"},"reference-count":28,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coalition for Epidemic Preparedness Innovation","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,24]]},"abstract":"<jats:p>Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.<\/jats:p>","DOI":"10.1172\/jci.insight.146082","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T12:03:11Z","timestamp":1619092991000},"source":"Crossref","is-referenced-by-count":13,"title":["Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-9984","authenticated-orcid":true,"given":"Ami","family":"Patel","sequence":"first","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4627-1354","authenticated-orcid":true,"given":"Emma L.","family":"Reuschel","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-7029","authenticated-orcid":true,"given":"Ziyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."},{"name":"Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faraz I.","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana P.","family":"Scott","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janess","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-4937","authenticated-orcid":true,"given":"Stephanie","family":"Ramos","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Feldmann","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7779-3059","authenticated-orcid":true,"given":"Atsushi","family":"Okumura","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Meade-White","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-227X","authenticated-orcid":true,"given":"Elaine","family":"Haddock","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Thomas","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-7423","authenticated-orcid":true,"given":"Rebecca","family":"Rosenke","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Lovaglio","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-1818","authenticated-orcid":true,"given":"Patrick W.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Saturday","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-2065","authenticated-orcid":true,"given":"Kar","family":"Muthumani","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9448-8227","authenticated-orcid":true,"given":"Heinz","family":"Feldmann","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent M.","family":"Humeau","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate E.","family":"Broderick","sequence":"additional","affiliation":[{"name":"Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60982-4"},{"key":"B2","unstructured":"WHO. Middle East Respiratory Syndrome Updates. http:\/\/www.emro.who.int\/health-topics\/mers-cov\/mers-outbreaks.html Accessed April 6, 2021"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.4178\/epih\/e2015033","article-title":"2015 MERS outbreak in Korea: hospital-to-hospital transmission","volume":"37","author":"Ki","year":"2015","journal-title":"Epidemiol Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2432"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.01568","article-title":"A review of DNA vaccines against influenza","volume":"9","author":"Lee","year":"2018","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac7462"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30266-X"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00103-019-03061-2"},{"key":"B9","article-title":"Safety and immunogenicity of an anti-Zika virus DNA vaccine \u2014 preliminary report","author":"Tebas","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz132"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.137079"},{"issue":"9","key":"B12","article-title":"Understanding the T cell immune response in SARS coronavirus infection","volume":"1","author":"Janice Oh","year":"2012","journal-title":"Emerg Microbes Infect"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aan5393"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.015"},{"key":"B15","doi-asserted-by":"crossref","unstructured":"Robbiani DF, et al. Convergent antibody responses to SARS-CoV-2 infection in convalescent individuals [preprint]. https:\/\/doi.org\/10.1101\/2020.05.13.092619 Posted on bioRxiv May 22, 2020","DOI":"10.1101\/2020.05.13.092619"},{"key":"B16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.antiviral.2015.07.005","article-title":"Animal models of Middle East respiratory syndrome coronavirus infection","volume":"122","author":"van Doremalen","year":"2015","journal-title":"Antiviral Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310744110"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.08.031"},{"key":"B19","article-title":"Evaluation of candidate vaccine approaches for MERS-CoV","volume":"6","author":"Wang","year":"2015","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba8399"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8475"},{"issue":"8","key":"B22","doi-asserted-by":"crossref","first-page":"e00227","DOI":"10.1128\/IAI.00227-19","article-title":"Intradermal synthetic DNA vaccination generates Leishmania-specific T cells in the skin and protection against Leishmania major","volume":"87","author":"Louis","year":"2019","journal-title":"Infect Immun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2015.020"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz137"},{"issue":"4","key":"B25","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.123158","article-title":"Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection","volume":"4","author":"Liu","year":"2019","journal-title":"JCI Insight"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1215691"},{"issue":"5","key":"B27","first-page":"389","article-title":"Thoracic radiography as a refinement methodology for the study of H1N1 influenza in cynomologus macaques (Macaca fascicularis)","volume":"60","author":"Brining","year":"2010","journal-title":"Comp Med"},{"issue":"39","key":"B28","doi-asserted-by":"crossref","DOI":"10.2807\/ese.17.39.20285-en","article-title":"Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction","volume":"17","author":"Corman","year":"2012","journal-title":"Euro Surveill"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/146082\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:43:37Z","timestamp":1779151417000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/146082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,24]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5,24]]},"published-print":{"date-parts":[[2021,5,24]]}},"alternative-id":["10.1172\/jci.insight.146082"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.146082","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,24]]},"article-number":"e146082"}}