Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Virol Sin. 2022 Oct;37(5):731-739. doi: 10.1016/j.virs.2022.06.002. Epub 2022 Jun 6.
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 Shingrix™ 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 Shingrix™ in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to Shingrix™ 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 Shingrix™ in a VZV-primed mouse model that was adopted for preclinical studies of Shingrix™. 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 Shingrix™ 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.
潜伏的水痘带状疱疹病毒（VZV）可能被激活，导致带状疱疹，一生中每三人就有一人会受到影响。目前可用的亚单位疫苗 Shingrix™ 在安全性和有效性方面均优于减毒疫苗 Zostavax®，但其关键佐剂成分 QS21 的供应有限。我们使用最近被 FDA 批准用于 COVID-19 mRNA 疫苗的可离子化脂质纳米颗粒（LNPs）作为载体，以及被 FDA 批准用于亚单位乙型肝炎疫苗的含 CpG 基序的寡脱氧核苷酸（CpG ODN）作为免疫刺激剂，开发了一种包裹 VZV-糖蛋白 E（gE）和 CpG ODN 的 LNPs 疫苗，并在 C57BL/6J 小鼠中比较了其与 Shingrix™的免疫原性。结果表明，通过酶联免疫吸附试验（ELISA）测定，LNP 疫苗诱导的 gE 特异性 IgG 抗体水平与 Shingrix™相当。最重要的是，LNP 疫苗诱导的细胞介导免疫（CMI）水平与 Shingrix™相当，在用于 Shingrix™临床前研究的 VZV 预致敏小鼠模型中，CMI 对带状疱疹疫苗的疗效起着决定性作用。在 LNP-CpG 佐剂的 VZV-gE 疫苗接种小鼠中，IL-2 和 IFN-γ 分泌的脾细胞数量以及表达 Th1 细胞因子的 CD4 T 细胞的比例与 Shingrix™增强小鼠相似。LNP 疫苗中的所有成分都可以大量人工和经济地合成，表明 LNP-CpG 佐剂的 VZV-gE 作为一种更具成本效益的带状疱疹疫苗具有潜力。
