PDF(Pubmed)
Abstract：
UNASSIGNED: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.
UNASSIGNED: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.
UNASSIGNED: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.
UNASSIGNED: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.
UNASSIGNED: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.
UNASSIGNED: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.
UNASSIGNED: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.
摘要：
使用不同疫苗平台的异源免疫已被证明是增强抗原特异性免疫应答的有效策略。在这项研究中,我们对中年小鼠水痘-带状疱疹病毒（VZV）的mRNA疫苗和佐剂蛋白亚单位疫苗的不同初免-加强免疫方案诱导的体液和细胞免疫应答进行了正面比较，旨在更好地了解疫苗接种计划对免疫反应的影响。
■合成VZV糖蛋白(gE)mRNA并包封到基于SM-102的脂质纳米颗粒(LNP)中。然后使用VZVgEmRNA疫苗（RNA-gE）和蛋白质亚单位疫苗（PS-gE）对VZV引发的中年C57BL/6小鼠进行同源和异源引发加强免疫策略。使用酶联免疫吸附测定（ELISA）分析评估抗原特异性抗体。此外,使用ELISPOT测定和流式细胞术检测细胞介导的免疫（CMI）。此外,还评估并比较了体内安全性.
负载mRNA的脂质纳米颗粒具有约130nm的流体动力学直径和0.156的多分散指数。总IgG抗体水平在不同免疫策略之间没有显着差异。然而,接受2×RNA-gE或RNA-gE>PS-gE的小鼠显示比接受2×PS-gE和PS-gE>RNA-gE的小鼠更低的IgG1/IgG2c比率。2×RNA-gE或RNA-gE>PS-gE诱导的CMI应答明显强于2×PS-gE和PS-gE>RNA-gE诱导的CMI应答。安全性评价表明mRNA疫苗和蛋白质疫苗均诱导小鼠短暂的体重减轻。此外，蛋白质疫苗在注射部位产生明显的炎症反应，而mRNA疫苗没有显示可观察到的炎症。
■异源初免-加强策略已经证明，在中年小鼠中，mRNA引发的免疫方案比蛋白质亚基引发的方案可以诱导更好的细胞介导的免疫应答。这些发现为VZV疫苗的设计和优化提供了有价值的见解，并有可能在未来扩大水痘疫苗接种策略。
■合成VZV糖蛋白(gE)mRNA并包封到基于SM-102的脂质纳米颗粒(LNP)中。然后使用VZVgEmRNA疫苗（RNA-gE）和蛋白质亚单位疫苗（PS-gE）对VZV引发的中年C57BL/6小鼠进行同源和异源引发加强免疫策略。使用酶联免疫吸附测定（ELISA）分析评估抗原特异性抗体。此外,使用ELISPOT测定和流式细胞术检测细胞介导的免疫（CMI）。此外,还评估并比较了体内安全性.
负载mRNA的脂质纳米颗粒具有约130nm的流体动力学直径和0.156的多分散指数。总IgG抗体水平在不同免疫策略之间没有显着差异。然而,接受2×RNA-gE或RNA-gE>PS-gE的小鼠显示比接受2×PS-gE和PS-gE>RNA-gE的小鼠更低的IgG1/IgG2c比率。2×RNA-gE或RNA-gE>PS-gE诱导的CMI应答明显强于2×PS-gE和PS-gE>RNA-gE诱导的CMI应答。安全性评价表明mRNA疫苗和蛋白质疫苗均诱导小鼠短暂的体重减轻。此外，蛋白质疫苗在注射部位产生明显的炎症反应，而mRNA疫苗没有显示可观察到的炎症。
■异源初免-加强策略已经证明，在中年小鼠中，mRNA引发的免疫方案比蛋白质亚基引发的方案可以诱导更好的细胞介导的免疫应答。这些发现为VZV疫苗的设计和优化提供了有价值的见解，并有可能在未来扩大水痘疫苗接种策略。
