{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:21:16Z","timestamp":1790310076485,"version":"4.1.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T00:00:00Z","timestamp":1483401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,15]],"date-time":"2017-01-15T00:00:00Z","timestamp":1484438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Mayo Clinic Discovery Translation Fund"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed \u201csingle-cycle\u201d adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To test them as potential vaccines, we engineered RD and SC versions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A\/PR\/8\/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen\n            <jats:italic>in vitro<\/jats:italic>\n            . SC-Ad produced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A\/PR\/8\/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as \u201cneedle-free\u201d mucosal vaccines.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Most adenovirus vaccines that are being tested are replication-defective adenoviruses (RD-Ads). This work describes testing newer single-cycle adenovirus (SC-Ad) vectors that replicate transgenes to amplify protein production and immune responses. We show that SC-Ads generate markedly more influenza virus hemagglutinin protein and require substantially less vector to generate the same immune responses as RD-Ad vectors. SC-Ads therefore hold promise to be more potent vectors and vaccines than current RD-Ad vectors.\n          <\/jats:p>","DOI":"10.1128\/jvi.00720-16","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T01:23:24Z","timestamp":1478136204000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses"],"prefix":"10.1128","volume":"91","author":[{"given":"Catherine M.","family":"Crosby","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Matchett","sequence":"additional","affiliation":[{"name":"Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie S.","family":"Anguiano-Zarate","sequence":"additional","affiliation":[{"name":"Clinical Translational Sciences Graduate Program, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Parks","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry R.","family":"Pease","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Webby","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Barry","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"547","article-title":"Update: influenza activity\u2014United States and worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine","volume":"53","author":"CDC","year":"2004","unstructured":"CDC. 2004. Update: influenza activity\u2014United States and worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine. MMWR Morb Mortal Wkly Rep 53:547\u2013552.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_3_2","first-page":"613","article-title":"Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP)\u2014United States, 2012-13 influenza season","volume":"61","author":"CDC","year":"2012","unstructured":"CDC. 2012. Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP)\u2014United States, 2012-13 influenza season. MMWR Morb Mortal Wkly Rep 61:613\u2013618.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_4_2","first-page":"10","article-title":"Early estimates of seasonal influenza vaccine effectiveness\u2014United States, January 2015","volume":"64","author":"Flannery B","year":"2015","unstructured":"Flannery B Clippard J Zimmerman RK Nowalk MP Jackson ML Jackson LA Monto AS Petrie JG McLean HQ Belongia EA Gaglani M Berman L Foust A Sessions W Thaker SN Spencer S Fry AM Centers for Disease Control and Prevention . 2015. Early estimates of seasonal influenza vaccine effectiveness\u2014United States, January 2015. MMWR Morb Mortal Wkly Rep 64:10\u201315.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.23.1.66-72.1986"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830140414"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090350"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1343"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1637\/0005-2086-47.s3.905"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70295-X"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.10.077"},{"key":"e_1_3_2_12_2","volume-title":"Influenza fact sheet","author":"WHO","year":"2014","unstructured":"WHO. 2014. Influenza fact sheet. WHO, Geneva, Switzerland."},{"key":"e_1_3_2_13_2","volume-title":"Executive board 115th session agenda item 4.17, Geneva Switzerland","author":"WHO","year":"2004","unstructured":"WHO. 2004. Influenza pandemic preparedness and response. Executive board 115th session agenda item 4.17, Geneva Switzerland, 11\u201312 November 2004. WHO, Geneva, Switzerland."},{"key":"e_1_3_2_14_2","volume-title":"Vaccines for pandemic influenza: informal meeting of WHO, influenza vaccine manufactures, national licensing agencies, and government representatives on influenza pandemic vaccines, Geneva, Switzerland","author":"WHO","year":"2004","unstructured":"WHO. 2004. Vaccines for pandemic influenza: informal meeting of WHO, influenza vaccine manufactures, national licensing agencies, and government representatives on influenza pandemic vaccines, Geneva, Switzerland, 11\u201312 November 2004. WHO, Geneva, Switzerland."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.07.093"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2011.03.001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.10.6333"},{"key":"e_1_3_2_18_2","first-page":"1","article-title":"Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)","volume":"48","author":"CDC","year":"1999","unstructured":"CDC. 1999. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 48:1\u201328.","journal-title":"MMWR Recomm Rep"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8456302"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11478"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240721"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/415331a"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2005.18.657"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2014.11.003"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(94)90264-X"},{"key":"e_1_3_2_26_2","first-page":"616","article-title":"Development of adenovirus vectors for the expression of heterologous genes","volume":"6","author":"Berkner KL","year":"1988","unstructured":"Berkner KL . 1988. Development of adenovirus vectors for the expression of heterologous genes. Biotechniques 6:616\u2013629.","journal-title":"Biotechniques"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-1669(99)00007-5"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2005.18.283"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02264-14"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00552-12"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073313"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.27238"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0696-0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.02.056"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018314"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.042508.093728"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e32833d2d2b"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-9-S2-P35"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70345-6"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.05.030"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02184-14"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3497"},{"key":"e_1_3_2_43_2","first-page":"169","article-title":"Use of the Syrian hamster as an animal model for oncolytic adenovirus vectors","volume":"130","author":"Thomas MA","year":"2007","unstructured":"Thomas MA Spencer JF Wold WS . 2007. Use of the Syrian hamster as an animal model for oncolytic adenovirus vectors. Methods Mol Med 130:169\u2013183.","journal-title":"Methods Mol Med"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a071545"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2007.0017"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.07.022"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.07.043"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.16.10200-10209.2005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005059"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2009.6"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00720-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00720-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:23:41Z","timestamp":1646490221000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00720-16"}},"subtitle":[],"editor":[{"given":"Terence S.","family":"Dermody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,1,15]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,1,15]]}},"alternative-id":["10.1128\/JVI.00720-16"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00720-16","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,15]]},"assertion":[{"value":"2016-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00720-16"}}