A Synergistic Lipid Nanoparticle Encapsulating mRNA Shingles Vaccine Induces Potent Immune Responses and Protects Guinea Pigs from Viral Challenges,Advanced Materials

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A Synergistic Lipid Nanoparticle Encapsulating mRNA Shingles Vaccine Induces Potent Immune Responses and Protects Guinea Pigs from Viral Challenges
Advanced Materials ( IF 27.4 ) Pub Date : 2023-12-25 , DOI: 10.1002/adma.202310886
Xingdi Cheng _{1,

2} , Sujia Liu ₃ , Jing Sun ₄ , Lin Liu ₃ , Xinghuan Ma ₃ , Jingjiao Li _{1,

2} , Bangda Fan ₃ , Chen Yang _{1,

2} , Yuanyuan Zhao _{1,

2} , Shuai Liu ₁ , Yixing Wen _{1,

2} , Wei Li _{1,

2} , Simin Sun ₁ , Shiwei Mi _{1,

2} , Haonan Huo _{1,

2} , Lei Miao ₅ , Hao Pan ₆ , Xiaolan Cui ₄ , Jiaqi Lin ₃ , Xueguang Lu _{1,

2}

Affiliation

Shingles is caused by the reactivation of varicella zoster virus (VZV) and manifests as painful skin rashes. While the recombinant protein-based vaccine proves highly effective, it encounters supply chain challenges due to a shortage of the necessary adjuvant. Messenger RNA (mRNA)-based vaccines can be rapidly produced on a large scale, but their effectiveness relies on efficient delivery and sequence design. Here, an mRNA-based VZV vaccine using a synergistic lipid nanoparticle (Syn-LNP) containing two different ionizable lipids is developed. Syn-LNP shows superior mRNA expression compared to LNPs formulated with either type of ionizable lipid and to a commercialized LNP. After encapsulating VZV glycoprotein E (gE)-encoding mRNA, mgE@Syn-LNP induces robust humoral and cellular immune responses in two strains of mice. The magnitude of these responses is similar to that induced by adjuvanted recombinant gE proteins and significantly higher than that observed with live-attenuated VZV. mgE@Syn-LNP exhibits durable humoral responses for over 7 months without obvious adverse effects. In addition, mgE@Syn-LNP protects vaccinated guinea pigs against live VZV challenges. Preliminary studies on the mRNA antigen design reveal that the removal of glycosylation sites of gE greatly reduces its immune responses. Collectively, Syn-LNP encapsulating gE-encoded mRNA holds great promise as a shingles vaccine.

中文翻译：

封装 mRNA 带状疱疹疫苗的协同脂质纳米颗粒可诱导有效的免疫反应并保护豚鼠免受病毒攻击

带状疱疹是由水痘带状疱疹病毒 (VZV) 重新激活引起的，表现为疼痛的皮疹。虽然基于重组蛋白的疫苗被证明非常有效，但由于缺乏必要的佐剂，它遇到了供应链挑战。基于信使 RNA (mRNA) 的疫苗可以快速大规模生产，但其有效性依赖于高效的递送和序列设计。在这里，开发了一种基于 mRNA 的 VZV 疫苗，使用含有两种不同的可电离脂质的协同脂质纳米颗粒 (Syn-LNP)。与用任一类型的可电离脂质配制的 LNP 和商业化的 LNP 相比，Syn-LNP 显示出优异的 mRNA 表达。在封装 VZV 糖蛋白 E (gE) 编码 mRNA 后，mgE@Syn-LNP 在两种小鼠品系中诱导强烈的体液和细胞免疫反应。这些反应的强度与含佐剂的重组 gE 蛋白诱导的反应相似，并且显着高于用减毒活 VZV 观察到的反应。 mgE@Syn-LNP 表现出超过 7 个月的持久体液反应，没有明显的副作用。此外，mgE@Syn-LNP 可以保护接种疫苗的豚鼠免受活水痘带状疱疹病毒的攻击。对mRNA抗原设计的初步研究表明，去除gE的糖基化位点会大大降低其免疫反应。总的来说，封装 gE 编码 mRNA 的 Syn-LNP 作为带状疱疹疫苗具有广阔的前景。

更新日期：2023-12-25

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