{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:17:32Z","timestamp":1767212252818,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32070932","31770184","2020GG0233"],"award-info":[{"award-number":["32070932","31770184","2020GG0233"]}]},{"name":"Science and Technology Plan Project of the Inner Mongolia Autonomous Region, China","award":["32070932","31770184","2020GG0233"],"award-info":[{"award-number":["32070932","31770184","2020GG0233"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-\u03b3+ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-\u03b3 (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8+ T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.<\/jats:p>","DOI":"10.3390\/v14061214","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T08:01:18Z","timestamp":1654243278000},"page":"1214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Jie","family":"Liu","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyang","family":"Lin","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linjun","family":"Cai","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Ding","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cenrong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Wu","sequence":"additional","affiliation":[{"name":"Animal Experiment Center, Changchun BCHT Biotechnology Co., Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Gao","sequence":"additional","affiliation":[{"name":"Animal Experiment Center, Changchun BCHT Biotechnology Co., Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-7423","authenticated-orcid":false,"given":"Weiheng","family":"Su","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlai","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrmicro3215","article-title":"Molecular mechanisms of varicella zoster virus pathogenesis","volume":"12","author":"Zerboni","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1128\/CMR.00052-13","article-title":"Pathogenesis and current approaches to control of varicella-zoster virus infections","volume":"26","author":"Gershon","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.4065\/82.11.1341","article-title":"A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction","volume":"82","author":"Yawn","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"g2911","DOI":"10.1136\/bmj.g2911","article-title":"Quantification of risk factors for herpes zoster: Population based case-control study","volume":"348","author":"Forbes","year":"2014","journal-title":"BMJ"},{"key":"ref_5","first-page":"1","article-title":"Prevention of herpes zoster: Recommendations of the Advisory Committee on Immunization Practices (ACIP)","volume":"57","author":"Harpaz","year":"2008","journal-title":"MMWR Recomm. Rep. Morb. Mortal. Wkly. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.04.013","article-title":"Risk of Stroke\/Transient Ischemic Attack or Myocardial Infarction with Herpes Zoster: A Systematic Review and Meta-Analysis","volume":"26","author":"Zhang","year":"2017","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jim.2009.09.010","article-title":"Interferon-gamma release assay: A simple method for detection of varicella-zoster virus-specific cell-mediated immunity","volume":"351","author":"Otani","year":"2009","journal-title":"J. Immunol. Methods"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1128\/JVI.03445-13","article-title":"Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia","volume":"88","author":"Steain","year":"2014","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1086\/605611","article-title":"Varicella-Zoster virus\u2014Specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine","volume":"200","author":"Weinberg","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6776","DOI":"10.1016\/j.vaccine.2019.09.031","article-title":"VZV-specific cell-mediated immunity, but not humoral immunity, correlates inversely with the incidence of herpes zoster and the severity of skin symptoms and zoster-associated pain: The SHEZ study","volume":"37","author":"Asada","year":"2019","journal-title":"Vaccine"},{"key":"ref_11","first-page":"341","article-title":"VZV T cell-mediated immunity","volume":"342","author":"Weinberg","year":"2010","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa051016","article-title":"A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults","volume":"352","author":"Oxman","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1056\/NEJMoa1501184","article-title":"Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults","volume":"372","author":"Lal","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.vaccine.2015.09.073","article-title":"Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults","volume":"34","author":"Chlibek","year":"2016","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/infdis\/jis497","article-title":"A phase 1\/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults","volume":"206","author":"Clement","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1146\/annurev.mi.44.100190.000423","article-title":"Glycoproteins encoded by varicella-zoster virus: Biosynthesis, phosphorylation, and intracellular trafficking","volume":"44","author":"Grose","year":"1990","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/S0264-410X(01)00475-3","article-title":"Immunization with a DNA vaccine expressing a truncated form of varicella zoster virus glycoprotein E","volume":"20","author":"Hasan","year":"2002","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/iid3.297","article-title":"Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant","volume":"8","author":"Lee","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11262-004-7434-z","article-title":"Translation of varicella-zoster virus genes during human ganglionic latency","volume":"29","author":"Grinfeld","year":"2004","journal-title":"Virus Genes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7080","DOI":"10.1073\/pnas.95.12.7080","article-title":"Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency","volume":"95","author":"Lungu","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11893","DOI":"10.1128\/JVI.74.24.11893-11898.2000","article-title":"Varicella-zoster virus gene expression in latently infected and explanted human ganglia","volume":"74","author":"Kennedy","year":"2000","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.1093\/infdis\/jiy407","article-title":"Varicella-Zoster Virus and the Enteric Nervous System","volume":"218","author":"Gershon","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1073\/pnas.93.5.2122","article-title":"Expression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons","volume":"93","author":"Mahalingam","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1128\/JVI.02416-09","article-title":"Expression of varicella-zoster virus immediate-early regulatory protein IE63 in neurons of latently infected human sensory ganglia","volume":"84","author":"Zerboni","year":"2010","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/sj.bjc.6605542","article-title":"IE63-specific T-cell responses associate with control of subclinical varicella zoster virus reactivation in individuals with malignancies","volume":"102","author":"Malavige","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1002\/eji.200737648","article-title":"Phenotypic analysis of human CD4+ T cells specific for immediate-early 63 protein of varicella-zoster virus","volume":"37","author":"Jones","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3389\/fimmu.2015.00553","article-title":"Effector and Central Memory Poly-Functional CD4+ and CD8+ T Cells are Boosted upon ZOSTAVAX\u00ae Vaccination","volume":"6","author":"Sei","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/S0264-410X(01)00486-8","article-title":"Immunogenicity of a recombinant varicella-zoster virus gE-IE63 fusion protein, a putative vaccine candidate against primary infection and zoster reactivation","volume":"20","author":"Jacquet","year":"2002","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, M.A. (2019). A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines, 7.","DOI":"10.3390\/vaccines7020037"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1093\/cid\/cir334","article-title":"Clinical applications of DNA vaccines: Current progress","volume":"53","author":"Ferraro","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Daniels, R.W., Rossano, A.J., Macleod, G.T., and Ganetzky, B. (2014). Expression of multiple transgenes from a single construct using viral 2A peptides in Drosophila. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100637"},{"key":"ref_32","first-page":"e56255","article-title":"In Vivo Assay for Detection of Antigen-specific T-cell Cytolytic Function Using a Vaccination Model","volume":"129","author":"Haymaker","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1016\/j.vaccine.2012.01.088","article-title":"Cell-mediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice","volume":"30","author":"Dendouga","year":"2012","journal-title":"Vaccine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1016\/j.vaccine.2019.02.048","article-title":"Efficient induction of cell-mediated immunity to varicella-zoster virus glycoprotein E co-lyophilized with a cationic liposome-based adjuvant in mice","volume":"37","author":"Wui","year":"2019","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1086\/375828","article-title":"Identification of CD8+ T cell epitopes in the immediate early 62 protein (IE62) of varicella-zoster virus, and evaluation of frequency of CD8+ T cell response to IE62, by use of IE62 peptides after varicella vaccination","volume":"188","author":"Frey","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1002\/jmv.10318","article-title":"Measurement of cell-mediated immunity with a Varicella-Zoster Virus-specific interferon-gamma ELISPOT assay: Responses in an elderly population receiving a booster immunization","volume":"70","author":"Smith","year":"2003","journal-title":"J. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/bmj.321.7258.424","article-title":"Th1 and Th2 responses: What are they?","volume":"321","author":"Berger","year":"2000","journal-title":"BMJ"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/2051013616655980","article-title":"Efficacy of varicella (VZV) vaccination: An update for the clinician","volume":"4","author":"Wang","year":"2016","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1128\/jvi.69.7.4274-4282.1995","article-title":"The transcriptional regulatory proteins encoded by varicella-zoster virus open reading frames (ORFs) 4 and 63, but not ORF 61, are associated with purified virus particles","volume":"69","author":"Kinchington","year":"1995","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1093\/infdis\/jiu279","article-title":"Fold rise in antibody titers by measured by glycoprotein-based enzyme-linked immunosorbent assay is an excellent correlate of protection for a herpes zoster vaccine, demonstrated via the vaccine efficacy curve","volume":"210","author":"Gilbert","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.4049\/jimmunol.165.6.3031","article-title":"The dual role of IL-2 in the generation and maintenance of CD8+ memory T cells","volume":"165","author":"Dai","year":"2000","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/978-1-4419-6451-9_3","article-title":"The role of interleukin-2 in memory CD8 cell differentiation","volume":"684","author":"Boyman","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s12250-020-00261-y","article-title":"Immune Responses to Varicella-Zoster Virus Glycoprotein E Formulated with Poly(Lactic-co-Glycolic Acid) Nanoparticles and Nucleic Acid Adjuvants in Mice","volume":"36","author":"Wang","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.4110\/in.2018.18.e38","article-title":"Herpes Zoster DNA Vaccines with IL-7 and IL-33 Molecular Adjuvants Elicit Protective T Cell Immunity","volume":"18","author":"Kim","year":"2018","journal-title":"Immune Netw."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cao, H., Wang, Y., Luan, N., and Liu, C. (2021). Immunogenicity of Varicella-Zoster Virus Glycoprotein E Formulated with Lipid Nanoparticles and Nucleic Immunostimulators in Mice. Vaccines, 9.","DOI":"10.3390\/vaccines9040310"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1128\/JVI.03124-14","article-title":"Abortive intrabronchial infection of rhesus macaques with varicella-zoster virus provides partial protection against simian varicella virus challenge","volume":"89","author":"Meyer","year":"2015","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1006\/mpat.1993.1064","article-title":"A mouse model for varicella-zoster virus latency","volume":"15","author":"Wroblewska","year":"1993","journal-title":"Microb. Pathog."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Baird, N.L., Zhu, S., Pearce, C.M., and Viejo-Borbolla, A. (2019). Current In Vitro Models to Study Varicella Zoster Virus Latency and Reactivation. Viruses, 11.","DOI":"10.3390\/v11020103"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/6\/1214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:59Z","timestamp":1760138639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/6\/1214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["v14061214"],"URL":"https:\/\/doi.org\/10.3390\/v14061214","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,6,2]]}}}