Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, People's Republic of China.
Emerg Microbes Infect. 2024 Dec;13(1):2392661. doi: 10.1080/22221751.2024.2392661. Epub 2024 Sep 12.
mRNA platform holds promise for next-generation Varicella-zoster Virus (VZV) vaccine development due to its high potency at inducing strong T-cell response. Built upon the design of our 1st-generation VZV mRNA vaccine that encodes for full-length gE antigen, in this study we reported on a novel combinatorial strategy to further optimize the gE-encoding mRNA sequence through signal peptide replacement, C-terminal modification, and insertion of mRNA-stabilizing motif, which collectively contributed to significantly improved vaccine immunogenicity. In adult mice, aged mice, and immunocompromised mice, this optimized VZV mRNA vaccine showed strong superiority in multiple aspects including the induction of gE-specific antibodies, specific memory B-cell response, as well as Th1-type T-cell response.
mRNA 平台因其在诱导强烈 T 细胞反应方面的高效性，有望成为下一代水痘带状疱疹病毒（VZV）疫苗开发的平台。本研究基于我们第一代编码全长 gE 抗原的 VZV mRNA 疫苗的设计，报告了一种通过替换信号肽、修饰 C 端和插入 mRNA 稳定基序来进一步优化 gE 编码 mRNA 序列的新型组合策略，这些策略共同显著提高了疫苗的免疫原性。在成年小鼠、老年小鼠和免疫功能低下的小鼠中，这种优化的 VZV mRNA 疫苗在诱导 gE 特异性抗体、特异性记忆 B 细胞反应以及 Th1 型 T 细胞反应等多个方面表现出强大的优势。
