{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:17:48Z","timestamp":1770898668953,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Natural Science\u00a0Foundation-Joint Fund\u00a0of\u00a0Original Innovation\u00a0of\u00a0Haidian","award":["L202040"],"award-info":[{"award-number":["L202040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Herpes zoster (HZ) is one of two distinct syndromes caused by Varicella-zoster virus (VZV). A primary infection with VZV causes varicella in susceptible young children. After resolution of the primary infection, VZV establishes a lifelong latency within the cranial or dorsal root ganglia. With increasing age, family history of shingles, immunosuppression or other risk factors, there is a decline in the virus-specific T-cell-mediated immune (CMI) response which allows reactivation of latent VZV in the root ganglia resulting in HZ. There are currently two vaccines that have been approved to prevent HZ and postherpetic neuralgia (PHN) but one is a live attenuated vaccine, the protective effect of which is considered to decrease significantly with the age of the recipient. However, a recombinant subunit vaccine may provide targeted VZV-specific cellular and humoral immunity, giving it a more potent and longer-lasting protective effect against HZ. The current study reports the development of a novel adjuvant, BC02 (BCG CpG DNA compound adjuvants system 02), composed of Al(OH)3 inorganic salt adjuvant and BC01 (BCG CpG DNA compound adjuvants system 01), a Toll-like receptor 9 (TLR9) agonist. Immunogenicity and compatibility with recombinant VZV glycoprotein E (gE) in mice were studied. The BC02-adjuvanted gE experimental vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE glycoprotein and VZV-Oka in a mouse model. The efficient production and long-term persistence of gE and VZV-Oka-specific IFN-\u03b3, IL-2-specific T cells and memory B cells in the early (1W), middle (7W), middle-late (15W), and final (27W) immune stages were established. Results of fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests also showed that the BC02 adjuvanted-gE experimental vaccine induced mice to secrete neutralizing antibodies against clinically isolated VZV strains. In combination, the current data suggest that the BC02 compound adjuvant offers a strategy to induce an appropriately strong cellular and humoral immunity against the VZV gE protein subunit to improve vaccine efficacy.<\/jats:p>","DOI":"10.3390\/vaccines10040529","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:45:51Z","timestamp":1648590351000},"page":"529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-3375","authenticated-orcid":false,"given":"Junli","family":"Li","sequence":"first","affiliation":[{"name":"Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"},{"name":"Key Laboratory for Quality Research and Evaluation of Biological Products, National Medical Products Administration (NMPA), Beijing 102629, China"},{"name":"Key Laboratory of Research on Quality and Standardization of Biotech Products, National Health Commission (NHC), Beijing 102629, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"},{"name":"Key Laboratory for Quality Research and Evaluation of Biological Products, National Medical Products Administration (NMPA), Beijing 102629, China"},{"name":"Key Laboratory of Research on Quality and Standardization of Biotech Products, National Health Commission (NHC), Beijing 102629, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"},{"name":"School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guozhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"},{"name":"Key Laboratory for Quality Research and Evaluation of Biological Products, National Medical Products Administration (NMPA), Beijing 102629, China"},{"name":"Key Laboratory of Research on Quality and Standardization of Biotech Products, National Health Commission (NHC), Beijing 102629, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China"},{"name":"Key Laboratory for Quality Research and Evaluation of Biological Products, National Medical Products Administration (NMPA), Beijing 102629, China"},{"name":"Key Laboratory of Research on Quality and Standardization of Biotech Products, National Health Commission (NHC), Beijing 102629, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"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. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1056\/NEJMcp013211","article-title":"Clinical practice. Herpes zoster","volume":"347","author":"Gnann","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1056\/NEJMcp1302674","article-title":"Clinical practice: Herpes zoster","volume":"369","author":"Cohen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gater, A., Uhart, M., McCool, R., and Pr\u00e9aud, E. (2015). The humanistic, economic and societal burden of herpes zoster in Europe: A critical review. BMC Public Health, 15.","DOI":"10.1186\/s12889-015-1514-y"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.eurger.2016.01.007","article-title":"The role of vaccination in successful independent ageing","volume":"7","author":"McElhaney","year":"2016","journal-title":"Eur. Geriatr. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S228","DOI":"10.1086\/522159","article-title":"Vaccination against Herpes Zoster and Postherpetic Neuralgia","volume":"197","author":"Oxman","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.2174\/15680266113136660181","article-title":"Immune Senescence and Vaccination in the Elderly","volume":"13","author":"Lang","year":"2013","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/2051013615599151","article-title":"Herpes zoster epidemiology, management, and disease and economic burden in Europe: A multi-disciplinary perspective","volume":"3","author":"Johnson","year":"2015","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e004833","DOI":"10.1136\/bmjopen-2014-004833","article-title":"Systematic review of incidence and complications of herpes zoster: Towards a global perspective","volume":"4","author":"Kawai","year":"2014","journal-title":"BMJ Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4065\/mcp.2010.0618","article-title":"Herpes Zoster Recurrences More Frequent Than Previously Reported","volume":"86","author":"Yawn","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/infdis\/jis334","article-title":"Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population","volume":"15","author":"Tseng","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1056\/NEJMcp1403062","article-title":"Clinical practice. Postherpetic neuralgia","volume":"371","author":"Johnson","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_13","unstructured":"(2016, March 14). European Medicines Agency. Available online: https:\/\/www.ema.europa.eu."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1093\/cid\/cir970","article-title":"Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50\u201359 years","volume":"54","author":"Schmader","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1086\/528696","article-title":"Varicella-Zoster Virus\u2013Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine","volume":"197","author":"Levin","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1056\/NEJMoa1501184","article-title":"Efficacy of an adju-vanted herpes zoster subunit vaccine in older adults","volume":"372","author":"Lal","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1177\/1060028018758431","article-title":"Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine","volume":"52","author":"James","year":"2018","journal-title":"Ann. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1056\/NEJMoa1603800","article-title":"Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older","volume":"375","author":"Cunningham","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1177\/1753425919879997","article-title":"Unmethylated CpG motif-containing genomic DNA fragment of Bacillus calmette-guerin promotes macrophage functions through TLR9-mediated activation of NF-\u03baB and MAPKs signaling pathways","volume":"26","author":"Li","year":"2020","journal-title":"Innate Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6050","DOI":"10.1016\/j.vaccine.2021.08.103","article-title":"Unmethylated CpG motif-containing genomic DNA fragments of bacillus calmette-guerin improves immune response towards a DNA vaccine for COVID-19","volume":"39","author":"Zhou","year":"2021","journal-title":"Vaccine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/j.1574-695X.2010.00660.x","article-title":"The development and preliminary evaluation of a new Mycobacterium tuberculosis vaccine comprising Ag85b, HspX and CFP-10:ESAT-6 fusion protein with CpG DNA and aluminum hydroxide adjuvants","volume":"59","author":"Chen","year":"2010","journal-title":"FEMS Immunol Med. Microbiol."},{"key":"ref_23","first-page":"1177","article-title":"Immune effect of STAg combined with BCG-DNA and aluminum hydroxide adjuvant in mice","volume":"24","author":"Zhang","year":"2011","journal-title":"Chin. J. Biol."},{"key":"ref_24","first-page":"941","article-title":"Synergistic enhancement of macrophage innate immune response with BC02 complex adjuvant","volume":"31","author":"Li","year":"2018","journal-title":"Chin. J. Biol."},{"key":"ref_25","first-page":"11","article-title":"Analysis of synergistic enhancement of innate immune response by BC02 compound adjuvant components","volume":"35","author":"Li","year":"2022","journal-title":"Chin. J. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/viro.2000.0754","article-title":"Immune response to vaccinia virus recombinants expressing glycoproteins gE, gB, gH, and gL of Varicella-zoster virus","volume":"280","author":"Hainz","year":"2001","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1128\/jcm.28.11.2500-2506.1990","article-title":"Epitopes functional in neutralization of varicella-zoster virus","volume":"28","author":"Forghani","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/infdis\/160.6.919","article-title":"Cellular and Humoral Immunity to Varicella Zoster Virus Glycoproteins in Immune and Susceptible Human Subjects","volume":"160","author":"Giller","year":"1989","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1128\/jvi.65.3.1491-1495.1991","article-title":"Major histocompatibility complex restriction of T-cell responses to var-icella-zoster virus in guinea pigs","volume":"65","author":"Hayward","year":"1991","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1006\/viro.1994.1145","article-title":"Neutralization epitope of the varicella-zoster virus gH:gL glycoprotein complex","volume":"199","author":"Forghani","year":"1994","journal-title":"Virology"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1128\/CVI.00250-14","article-title":"Detection of antibodies to varicellazoster virus in recipients of the varicella vaccine by using a luciferase immunoprecipitation system assay","volume":"21","author":"Cohen","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jviromet.2011.04.014","article-title":"Recombinant glycoprotein E produced in mammalian cells in large-scale as an antigen for varicel-la-zoster-virus serology","volume":"175","author":"Thomsson","year":"2011","journal-title":"J. Virol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7087","DOI":"10.1016\/j.vaccine.2007.07.051","article-title":"Phenotypic and functional characterization of ex vivo T cell responses to the live attenuated herpes zoster vaccine","volume":"25","author":"Levin","year":"2007","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.vaccine.2011.11.096","article-title":"Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults \u226560 years of age","volume":"30","author":"Vermeulen","year":"2012","journal-title":"Vaccine"},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1093\/infdis\/jiy095","article-title":"Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older","volume":"217","author":"Cunningham","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.4049\/jimmunol.1400948","article-title":"Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells","volume":"193","author":"Didierlaurent","year":"2014","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39475","DOI":"10.1038\/srep39475","article-title":"Central Role of CD169+ Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01","volume":"6","author":"Detienne","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41541-017-0027-3","article-title":"Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFN\u03b3 response promoting vaccine immunogenicity","volume":"2","author":"Coccia","year":"2017","journal-title":"NPJ Vaccines"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/infdis\/136.4.519","article-title":"Antibody to Varicella-Zoster Virus-Induced Membrane Antigen: Immunofluorescence Assay Using Monodisperse Glutaraldehyde-Fixed Target Cells","volume":"136","author":"Zaia","year":"1977","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1128\/jcm.16.5.878-884.1982","article-title":"Comparison of the Raji cell line fluorescent an-tibody to membrane antigen test and the enzyme-linked immunosorbent assay for determination of immunity to varicella-zoster virus","volume":"16","author":"Iltis","year":"1982","journal-title":"J. Clin. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/infdis\/130.6.669","article-title":"Serologic response to varicella-zoster membrane antigens measured by direct immunofluorescence","volume":"130","author":"Williams","year":"1974","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S147","DOI":"10.1086\/529448","article-title":"Use and Limitations of Varicella-Zoster Virus\u2013Specific Serological Testing to Evaluate Breakthrough Disease in Vaccinees and to Screen for Susceptibility to Varicella","volume":"197","author":"Breuer","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3349\/ymj.2014.55.2.459","article-title":"Evaluation of a commercial glycoprotein enzymelinked im-munosorbent assay for measuring vaccine immunity to varicella","volume":"55","author":"Kim","year":"2014","journal-title":"Yonsei Med. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0928-0197(94)90051-5","article-title":"Detection of antibodies to varicella-zoster virus using a latex agglutination assay","volume":"2","author":"Gershon","year":"1994","journal-title":"Clin. Diagn. Virol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/4\/529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:45:40Z","timestamp":1760136340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/4\/529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["vaccines10040529"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10040529","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]}}}