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Volume 37 Issue 5
October 2022

    . doi: 10.1016/j.virs.2022.06.002
    Citation: Ning Luan, Han Cao, Yunfei Wang, Kangyang Lin, Cunbao Liu. LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with ShingrixTM in VZV-primed mice .VIROLOGICA SINICA, 2022, 37(5) : 731-739.  http://dx.doi.org/10.1016/j.virs.2022.06.002
    shu

    LNP-CpG ODN佐剂的水痘-带状疱疹病毒糖蛋白E在VZV初免的小鼠中诱导与ShingrixTM相当的免疫水平

    • 中国医学科学院医学生物学研究所

    • 通讯作者： 刘存宝, cunbao_liu@163.com
    • 收稿日期： 2022-03-02
      录用日期： 2022-06-01
    • 潜伏感染的水痘-带状疱疹病毒（VZV）重新激活可能导致带状疱疹，人一生中得带状疱疹的概率为1/3。目前上市的亚单位疫苗ShingrixTM在安全性和有效性方面均优于减毒活疫苗Zostavax®，但其关键佐剂成分QS21的供应有限。我们使用FDA最近批准用于COVID-19 mRNA疫苗的可电离脂质纳米颗粒（LNP）作为载体，以及FDA批准用于乙型肝炎亚单位疫苗的富含GC的单链寡聚脱氧核苷酸片段（CpG ODN）作为免疫刺激剂，开发了包裹VZV-糖蛋白E和CpG ODN的LNP疫苗，并在C57BL/6J小鼠中比较了其与ShingrixTM的免疫原性。酶联免疫吸附实验（ELISA）表明，LNP疫苗诱导了与ShingrixTM相当的gE特异性IgG抗体水平。最重要的是，在用于ShingrixTM临床前评价的VZV初免的小鼠模型中，LNP疫苗诱导了与ShingrixTM相当水平的细胞免疫应答（CMI），而CMI对于ShingrixTM的功效起决定性作用。这些CMI指标包括酶联免疫斑点（ELISPOT）实验检测到的分泌IL-2和IFN-γ的脾细胞数量，以及通过流式细胞术检测到的分泌T辅助细胞1（Th1）细胞因子的CD4+细胞比例。该LNP疫苗中的所有组分都可以人工和经济地大量合成，具有作为更具成本效益的带状疱疹疫苗的潜力。

    LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with ShingrixTM in VZV-primed mice

    • Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China

    • Corresponding author: Cunbao Liu, cunbao_liu@163.com
    • Received Date: 02 March 2022
      Accepted Date: 01 June 2022
    • Latent varicella-zoster virus (VZV) may be reactivated to cause herpes zoster, which affects one in three people during their lifetime. The currently available subunit vaccine ShingrixTM is superior to the attenuated vaccine Zostavax® in terms of both safety and efficacy, but the supply of its key adjuvant component QS21 is limited. With ionizable lipid nanoparticles (LNPs) that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers, and oligodeoxynucleotides containing CpG motifs (CpG ODNs) approved by the FDA for a subunit hepatitis B vaccine as immunostimulators, we developed a LNP vaccine encapsulating VZV-glycoprotein E (gE) and CpG ODN, and compared its immunogenicity with ShingrixTM in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to ShingrixTM as determined by enzyme-linked immunosorbent assay (ELISA). Most importantly, the LNP vaccine induced comparable levels of cell-mediated immunity (CMI) that plays decisive roles in the efficacy of zoster vaccines to ShingrixTM in a VZV-primed mouse model that was adopted for preclinical studies of ShingrixTM. Number of IL-2 and IFN-γ secreting splenocytes and proportion of T helper 1 (Th1) cytokine-expressing CD4+ T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of ShingrixTM boosted mice. All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities, indicating the potential of LNP-CpG-adjuvanted VZV-gE as a more cost-effective zoster vaccine.
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      LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with ShingrixTM in VZV-primed mice

        Corresponding author: Cunbao Liu, cunbao_liu@163.com
      • Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China
      • Received Date: 02 March 2022
      • Accepted Date: 01 June 2022

      Abstract: Latent varicella-zoster virus (VZV) may be reactivated to cause herpes zoster, which affects one in three people during their lifetime. The currently available subunit vaccine ShingrixTM is superior to the attenuated vaccine Zostavax® in terms of both safety and efficacy, but the supply of its key adjuvant component QS21 is limited. With ionizable lipid nanoparticles (LNPs) that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers, and oligodeoxynucleotides containing CpG motifs (CpG ODNs) approved by the FDA for a subunit hepatitis B vaccine as immunostimulators, we developed a LNP vaccine encapsulating VZV-glycoprotein E (gE) and CpG ODN, and compared its immunogenicity with ShingrixTM in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to ShingrixTM as determined by enzyme-linked immunosorbent assay (ELISA). Most importantly, the LNP vaccine induced comparable levels of cell-mediated immunity (CMI) that plays decisive roles in the efficacy of zoster vaccines to ShingrixTM in a VZV-primed mouse model that was adopted for preclinical studies of ShingrixTM. Number of IL-2 and IFN-γ secreting splenocytes and proportion of T helper 1 (Th1) cytokine-expressing CD4+ T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of ShingrixTM boosted mice. All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities, indicating the potential of LNP-CpG-adjuvanted VZV-gE as a more cost-effective zoster vaccine.

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