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一种自我放大mRNA疫苗的模块化设计,用于针对Neisseria meningitidis B的多价值免疫

Geng Chen¹, Geng Chen², Shanshan Wang³

¹Ningbo Junjian Biotechnologies Co., Ltd., Ningbo 315832, PR China.

|November 8, 2025

概括

自强化mRNA (SAM) 疫苗对尼塞利亚脑膜炎 B 组呈现有前途的表现.混合输送的SAM疫苗优于双重构造,诱导强大的免疫反应,并为细菌疫苗提供剂量节约的潜力.

科学领域:

疫苗学疫苗学疫苗学
微生物病原体的产生
分子生物学分子生物学

背景情况:

由于抗原的多样性,Neisseria meningitidis B组 (MenB) 存在重大疫苗开发挑战.
自放大mRNA (SAM) 疫苗平台为持续的抗原表达和多价抗原递送提供了潜力.
现有的MenB疫苗在覆盖多种菌株和引起广泛免疫力方面存在局限性.

研究的目的:

构建和评估两种不同的多价值SAM疫苗设计,以对抗MenB.
为了比较协同融合SAM构造的免疫性和表达水平与单独交付的SAM.
评估不同SAM交付策略的可制造性和标准化优势.

主要方法:

构建一个单一的融合SAM编码四个MenB抗原 (fHbp,NHBA,Nada,PorA).
为单个抗原开发四个单独的SAM结构,通过封装前混合 (PreMix) 或封装后混合 (PostMix) 交付.
在小鼠体外表达的评估,血清杀菌试验 (SBA) 标位,以及幽默/细胞免疫反应.

主要成果:

双重SAM结构在体外表达有限,但诱导了免疫反应.
单抗原混合输送SAM方法显示出优异的抗原表达和免疫性.
SAM-PreMix配方实现了高SBA标位 (1:256在5μg) 并诱导了低剂量 (1μg) 的强烈反应.
在可制造性和标准化方面,PreMix比PostMix提供了工艺优势.

结论:

作为单个抗原结构提供的多价值SAM疫苗优于MenB.的双重融合设计.
SAM平台,特别是PreMix配方,为开发多价值细菌疫苗提供了一种强效,剂量节省和可制造的方法.
这项技术为开发针对复杂细菌病原体的mRNA疫苗提供了通用策略.

关键词:

提供抗原的输送.免疫性免疫性免疫性小鼠免疫模型的免疫模型.这是一种多价值疫苗.尼塞利亚脑膜炎的血清组B.自强化的mRNA.

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