{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:59Z","timestamp":1760144219819,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T00:00:00Z","timestamp":1711843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2023YFC2307900","82161138001"],"award-info":[{"award-number":["2023YFC2307900","82161138001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation","award":["2023YFC2307900","82161138001"],"award-info":[{"award-number":["2023YFC2307900","82161138001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescence imaging and virus DNA tracking with real-time PCR. Luciferase activity and virus DNA were mainly found in the liver and spleen after the intravenous administration of SAdV1-GFluc. The results of flow cytometry illustrated that macrophages in the liver and spleen as well as hepatocytes were the target cells. Repeated inoculation was noneffective because of the stimulated serum neutralizing antibodies (NAbs) against SAdV-1. A transient, local expression of low-level luciferase was detected after intragastric administration, and the administration could be repeated without compromising the expression of the reporter gene. Intranasal administration led to a moderate, constant expression of a transgene in the whole respiratory tract and could be repeated one more time without a significant increase in the NAb titer. An immunohistochemistry assay showed that respiratory epithelial cells and macrophages in the lungs were transduced. High luciferase activity was restricted at the injection site and sustained for a week after intramuscular administration. A compromised transgene expression was observed after a repeated injection. When these mice were intramuscularly injected for a third time with the human adenovirus 5 (HAdV-5) vector carrying a luciferase gene, the luciferase activity recovered and reached the initial level, suggesting that the sequential use of SAdV-1 and HAdV-5 vectors was practicable. In short, the intranasal inoculation or intramuscular injection may be the preferred administration routes for the novel SAdV-1 vector in vaccine development.<\/jats:p>","DOI":"10.3390\/v16040550","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:44:52Z","timestamp":1711892692000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Biodistribution of Replication-Defective Simian Adenovirus 1 Vector in a Mouse Model"],"prefix":"10.3390","volume":"16","author":[{"given":"Juan","family":"Chen","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"},{"name":"School of Public Health, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1960-183X","authenticated-orcid":false,"given":"Xiaojuan","family":"Guo","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6834-1341","authenticated-orcid":false,"given":"Xiaohui","family":"Zou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlei","family":"Yang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"},{"name":"Henan Chemical Technician College, Kaifeng 475008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhe","family":"Hou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matvey V.","family":"Sprindzuk","sequence":"additional","affiliation":[{"name":"United Institute of Informatics Problems, National Academy of Sciences of Belarus, 220012 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5767-401X","authenticated-orcid":false,"given":"Zhuozhuang","family":"Lu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"001721","DOI":"10.1099\/jgv.0.001721","article-title":"ICTV Virus Taxonomy Profile: Adenoviridae 2022","volume":"103","author":"Benko","year":"2022","journal-title":"J. Gen. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Nishikawaji, Y., Kawakami, H., and Kosai, K.I. (2021). Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy. Viruses, 13.","DOI":"10.3390\/v13122502"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/hum.2013.2527","article-title":"Adenovirus: The first effective in vivo gene delivery vector","volume":"25","author":"Crystal","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fougeroux, C., and Holst, P.J. (2017). Future Prospects for the Development of Cost-Effective Adenovirus Vaccines. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040686"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.coviro.2021.03.006","article-title":"Adenovirus\u2014A blueprint for gene delivery","volume":"48","author":"Greber","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3201\/eid2301.161297","article-title":"Acute Respiratory Disease in US Army Trainees 3 Years after Reintroduction of Adenovirus Vaccine","volume":"23","author":"Clemmons","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0264-410X(96)00012-6","article-title":"Human adenovirus type 5 vectors expressing rabies glycoprotein","volume":"14","author":"Yarosh","year":"1996","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lundstrom, K. (2023). Viral Vectors in Gene Therapy: Where Do We Stand in 2023?. Viruses, 15.","DOI":"10.3390\/v15030698"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2338","DOI":"10.1002\/rmv.2338","article-title":"Human adenovirus type 26 basic biology and its usage as vaccine vector","volume":"32","author":"Majhen","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2002083","DOI":"10.1080\/21645515.2021.2002083","article-title":"A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson","volume":"18","author":"Patel","year":"2022","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_11","first-page":"776","article-title":"Chimpanzee Adenovirus Vector Ebola Vaccine--Preliminary Report","volume":"373","author":"Ledgerwood","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0140-6736(20)31605-6","article-title":"Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: A randomised, double-blind, placebo-controlled, phase 2 trial","volume":"396","author":"Zhu","year":"2020","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.4161\/hv.29594","article-title":"Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what\u2019s important?","volume":"10","author":"Kobinger","year":"2014","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/jcb.22328","article-title":"The influence of innate and pre-existing immunity on adenovirus therapy","volume":"108","author":"Zaiss","year":"2009","journal-title":"J. Cell Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yan, B., Zou, X., Liu, X., Zhao, J., Zhang, W., Guo, X., Wang, M., Lv, Y., and Lu, Z. (2020). User-Friendly Reverse Genetics System for Modification of the Right End of Fowl Adenovirus 4 Genome. Viruses, 12.","DOI":"10.3390\/v12030301"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1080\/21645515.2017.1419108","article-title":"Development of novel vaccine vectors: Chimpanzee adenoviral vectors","volume":"14","author":"Guo","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e01924-17","DOI":"10.1128\/JVI.01924-17","article-title":"Rapid Cloning of Novel Rhesus Adenoviral Vaccine Vectors","volume":"92","author":"Abbink","year":"2018","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1080\/14760584.2017.1394842","article-title":"Chimpanzee adenoviral vectors as vaccines\u2013challenges to move the technology into the fast lane","volume":"16","author":"Vitelli","year":"2017","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102282","DOI":"10.1016\/j.coi.2023.102282","article-title":"Cell entry and innate sensing shape adaptive immune responses to adenovirus-based vaccines","volume":"80","author":"Vijayan","year":"2023","journal-title":"Curr. Opin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Besson, S., Vragniau, C., Vassal-Stermann, E., Dagher, M.C., and Fender, P. (2020). The Adenovirus Dodecahedron: Beyond the Platonic Story. Viruses, 12.","DOI":"10.3390\/v12070718"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1002\/1873-3468.13700","article-title":"Lessons learned from adenovirus (1970\u20132019)","volume":"593","author":"Nemerow","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tips.2012.04.005","article-title":"Adenovirus receptors: Implications for targeting of viral vectors","volume":"33","author":"Arnberg","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13699","DOI":"10.1073\/pnas.1920896117","article-title":"Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry","volume":"117","author":"Suomalainen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/mmi.14909","article-title":"Adenovirus entry: Stability, uncoating, and nuclear import","volume":"118","author":"Greber","year":"2022","journal-title":"Mol. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Guo, X., Sun, Y., Chen, J., Zou, X., Hou, W., Tan, W., Hung, T., and Lu, Z. (2022). Restriction-Assembly: A Solution to Construct Novel Adenovirus Vector. Viruses, 14.","DOI":"10.3390\/v14030546"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1099\/vir.0.80757-0","article-title":"Complete genome sequence of simian adenovirus 1: An Old World monkey adenovirus with two fiber genes","volume":"86","author":"Kovacs","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_27","unstructured":"He, T.C. (2004). Current Protocols in Human Genetics, John Wiley & Sons, Inc.. Chapter 12, Unit 12."},{"key":"ref_28","first-page":"389","article-title":"Construction of first-generation adenoviral vectors","volume":"69","author":"Ng","year":"2002","journal-title":"Methods Mol. Med."},{"key":"ref_29","first-page":"515","article-title":"Construction of adenoviral vectors","volume":"135","author":"Davis","year":"2000","journal-title":"Methods Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00705-012-1293-z","article-title":"Construction of an infectious clone of human adenovirus type 41","volume":"157","author":"Chen","year":"2012","journal-title":"Arch. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Keyaerts, M., Remory, I., Caveliers, V., Breckpot, K., Bos, T.J., Poelaert, J., Bossuyt, A., and Lahoutte, T. (2012). Inhibition of firefly luciferase by general anesthetics: Effect on in vitro and in vivo bioluminescence imaging. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030061"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1016\/j.vaccine.2016.09.043","article-title":"Prevalence of serum neutralizing antibodies to adenovirus type 5 (Ad5) and 41 (Ad41) in children is associated with age and sanitary conditions","volume":"34","author":"Yang","year":"2016","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-1-0716-2128-8_7","article-title":"Isolation and Culture of Mouse Hepatocytes and Kupffer Cells (KCs)","volume":"2455","author":"Mendoza","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_34","first-page":"e56993","article-title":"Purification of Hepatocytes and Sinusoidal Endothelial Cells from Mouse Liver Perfusion","volume":"132","author":"Cabral","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vanekova, L., Polidarova, M.P., Veverka, V., Birkus, G., and Brazdova, A. (2022). Multiparametric Flow Cytometry-Based Immunophenotyping of Mouse Liver Immune Cells. Methods Protoc., 5.","DOI":"10.3390\/mps5050070"},{"key":"ref_36","first-page":"204","article-title":"New viral agents recovered from tissue cultures of monkey kidney cells. I. Origin and properties of cytopathogenic agents S.V.1, S.V.2, S.V.4, S.V.5, S.V.6, S.V.11, S.V.12 and S.V.15","volume":"63","author":"Hull","year":"1956","journal-title":"Am. J. Hyg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.3201\/eid1807.111665","article-title":"Adenoviruses in fecal samples from asymptomatic rhesus macaques, United States","volume":"18","author":"Roy","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.vetmic.2010.12.005","article-title":"Molecular characterization of adenoviruses in fecal samples of captively bred rhesus macaques in China","volume":"149","author":"Lu","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.vetmic.2009.10.014","article-title":"Molecular detection of novel adenoviruses in fecal specimens of captive monkeys with diarrhea in China","volume":"142","author":"Banyai","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lenman, A., Liaci, A.M., Liu, Y., Ardahl, C., Rajan, A., Nilsson, E., Bradford, W., Kaeshammer, L., Jones, M.S., and Frangsmyr, L. (2015). Human adenovirus 52 uses sialic acid-containing glycoproteins and the coxsackie and adenovirus receptor for binding to target cells. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004657"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E4264","DOI":"10.1073\/pnas.1716900115","article-title":"Polysialic acid is a cellular receptor for human adenovirus 52","volume":"115","author":"Lenman","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/104454903321908647","article-title":"Structure and chromosomal localization of the murine coxsackievirus and adenovirus receptor gene","volume":"22","author":"Chen","year":"2003","journal-title":"DNA Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1073\/pnas.94.7.3352","article-title":"HCAR and MCAR: The human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses","volume":"94","author":"Tomko","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1128\/JVI.72.1.415-419.1998","article-title":"The murine CAR homolog is a receptor for coxsackie B viruses and adenoviruses","volume":"72","author":"Bergelson","year":"1998","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/excr.1999.4761","article-title":"Expression of the adenovirus receptor and its interaction with the fiber knob","volume":"255","author":"Tomko","year":"2000","journal-title":"Exp. Cell Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/imm.12462","article-title":"Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus","volume":"145","author":"Guo","year":"2015","journal-title":"Immunology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"860399","DOI":"10.3389\/fimmu.2022.860399","article-title":"Differential Biodistribution of Adenoviral-Vectored Vaccine Following Intranasal and Endotracheal Deliveries Leads to Different Immune Outcomes","volume":"13","author":"Jeyanathan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S2213-2600(22)00087-X","article-title":"Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: A randomised, open-label, single-centre trial","volume":"10","author":"Li","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1479-0556-6-5","article-title":"Organ distribution of transgene expression following intranasal mucosal delivery of recombinant replication-defective adenovirus gene transfer vector","volume":"6","author":"Damjanovic","year":"2008","journal-title":"Genet. Vaccines Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.ymthe.2022.01.034","article-title":"Adenovirus-based vaccines-a platform for pandemic preparedness against emerging viral pathogens","volume":"30","author":"Coughlan","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1002\/1873-3468.13696","article-title":"Innate immunity to adenovirus: Lessons from mice","volume":"593","author":"Atasheva","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eabc6659","DOI":"10.1126\/scitranslmed.abc6659","article-title":"Systemic cancer therapy with engineered adenovirus that evades innate immunity","volume":"12","author":"Atasheva","year":"2020","journal-title":"Sci. Transl. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/4\/550\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:49Z","timestamp":1760106109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/4\/550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,31]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["v16040550"],"URL":"https:\/\/doi.org\/10.3390\/v16040550","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2024,3,31]]}}}