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causes two diseases: varicella upon primary infection and herpes zoster when latent viruses in the sensory ganglia reactivate. While varicella vaccines depend on humoral immunity to prevent VZV infection, cell-mediated immunity (CMI), which plays a therapeutic role in the control or elimination of reactivated VZV in infected cells, is decisive for zoster vaccine efficacy. As one of the most abundant glycoproteins of VZV, conserved glycoprotein E (gE) is essential for viral replication and transmission between ganglion cells, thus making it an ideal target subunit vaccine antigen; gE has been successfully used in the herpes zoster vaccine ShingrixTM on the market. In this report, we found that ionizable lipid nanoparticles (LNPs) approved by the Food and Drug Administration (FDA) as vectors for coronavirus disease 2019 (COVID-19) mRNA vaccines could enhance the synergistic adjuvant effect of CpG oligodeoxynucleotides (CpG ODNs) and QS21 on VZV-gE, affecting both humoral immunity and CMI. Vaccines made with these LNPs showed promise as varicella vaccines without a potential risk of herpes zoster, which identifies them as a novel type of herpes zoster vaccine similar to ShingrixTM. All of the components in this LNP-CpG-QS21 adjuvant system were proven to be safe after mass vaccination, and the high proportion of cholesterol contained in the LNPs was helpful for limiting the cytotoxicity induced by QS21, which may lead to the development of a novel herpes zoster subunit vaccine for clinical application.<\/jats:p>","DOI":"10.3390\/pharmaceutics14050973","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T07:08:58Z","timestamp":1651475338000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-7464","authenticated-orcid":false,"given":"Ning","family":"Luan","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Cao","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangyang","family":"Lin","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunbao","family":"Liu","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15016","DOI":"10.1038\/nrdp.2015.16","article-title":"Varicella zoster virus infection","volume":"1","author":"Gershon","year":"2015","journal-title":"Nat. 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