三款mRNA疫苗制备工艺技术分析

Analysis of Preparation Technology of Three mRNA Vaccines

与传统的灭活疫苗相比,mRNA疫苗免疫原性强,可同时激活体液免疫和细胞免疫,另外还具有开发周期短、广谱性、成本低和可大规模快速量产等优势,可有效应对突发性、变异快以及大规模的疫情。作为一种新的疫苗开发路径,mRNA疫苗在技术工艺上有很多新的特色和挑战。该研究以Pfizer/BioNTech公司的mRNA疫苗BNT162b2、Moderna公司的mRNA-1273,以及国内多家单位联合开发的ARCoV这3款新型冠状病毒疫苗为例,从抗原选择、核苷修饰及脂质体纳米颗粒(LNP)制剂制备等方面,对mRNA疫苗的开发设计和制备工艺进行了梳理分析,并讨论了当前面临的挑战和未来的发展方向,旨在为mRNA疫苗技术的开发和应用提供参考。

Compared with traditional inactivated vaccines,mRNA vaccines have strong immunogenicity and can activate both humoral and cellular immunity.In addition,it has the advantages of a short development cycle,broad neutralization breadth,low cost,and a relatively simple manufacturing process that can be rapidly scaled to respond to sudden and rapidly mutating pandemic outbreaks.As a new vaccine technology,mRNA vaccines have many novel features and challenges.Taking the three coronavirus disease 2019(COVID-19)vaccines,BNT162b2 from Pfizer/BioNTech,mRNA-1273 from Moderna,and ARCoV developed by several Chinese institutions,as examples,this paper summarizes and analyzes the development and manufacturing strategy for mRNA vaccines in terms of antigen selection,nucleoside modification,and lipid nanoparticles(LNP)formulation preparation.The current challenges and future directions are discussed to contribute to a better understanding of mRNA vaccine technology.