PDF(686 KB)
PDF(686 KB)
PDF(686 KB)
核酸疫苗研发态势与发展建议
Development Trends and Suggestions of Nucleic Acid Vaccines
应对新型冠状病毒肺炎（COVID-19）疫情防控的迫切需求，核酸疫苗以其快速高效的优点得到了疫苗研发领域的高度重视，特别是信使核糖核酸（mRNA）疫苗的研发进程显著加快，首次获批上市并在人体中使用。本文从核酸疫苗及相关技术概念、研发轨迹与发展趋势等方面总结梳理核酸疫苗的研发态势，辨识核酸疫苗特征，分析 COVID-19 疫情对 mRNA疫苗研究的促进作用，梳理核酸疫苗拓展应用的主要领域，针对可能存在的技术性、安全性问题开展深入讨论。研究建议，从改良目的基因表达、完善递送系统、提高免疫应答、增强 mRNA 稳定性及易存性等方面着手，着力开展核酸疫苗的关键技术开发；严格监管核酸疫苗的安全性和有效性；引导利益相关方对具有安全性风险、可能对肿瘤与传染病防控带来颠覆性影响的 mRNA 疫苗技术开展改进研究，注重技术研发的前瞻布局并促进应用转化。
Considering the urgent needs of coronavirus disease 2019 (COVID-19) epidemic prevention and control, nucleic acid vaccine has attracted great attention in the vaccine research and development (R&D) field owing to its high efficiency and good efficacy. Particularly, the R&D process of messenger RNA (mRNA) vaccine has significantly accelerated, and the mRNA vaccine was approved for the first time to be marketed and used in humans. This article first summarizes the R&D status of nucleic acid vaccines from the aspects of related technical concept, R&D path, and development trend, and identifies the characteristics of nucleic acid vaccines. Subsequently, it analyzes the impact of COVID-19 outbreak on the mRNA vaccine research, summarizes the main fields of application of nucleic acid vaccines, and studies the possible technical and safety problems. Furthermore, we suggest that the key technologies of nucleic acid vaccines should be developed by improving the target gene expression, delivery system, immune response, and mRNA stability and storage. Moreover, the safety and efficacy of nucleic acid vaccines should be strictly monitored; stakeholders should conduct research on mRNA vaccine technologies that have safety risks and potentially disruptive effects on cancer and infectious disease prevention and control; and a forward-looking technological layout and technical transformation should be emphasized.
核酸疫苗 / 脱氧核糖核酸（DNA）疫苗 / 核糖核酸（RNA）疫苗 / 信使核糖核酸（mRNA）疫苗 / 新型冠状病毒肺 炎 / 肿瘤
nucleic acid vaccine / deoxyribonucleic acid (DNA) vaccine / ribonucleic acid (RNA) vaccine / messenger RNA (mRNA) vaccine / coronavirus disease 2019 (COVID-19) / cancer
| [1] |
谢华玲, 陈芳, Liu C, 等. 全球疫苗研发态势分析 [J]. 中国生物 工程杂志, 2019, 39(5): 35–42. Xie H L, Chen F, Liu C, et al. Analysis of global vaccines development situation [J]. China Biotechnology, 2019, 39(5): 35–42.
|
| [2] |
杨益隆, 徐俊杰. 新型疫苗研发与下一代技术 [J]. 生物产业技 术, 2017 (2): 43–50. Yang Y L, Xu J J. Novel vaccine development and next generation technology of vaccine design [J]. Biotechnology & Business, 2017 (2): 43–50.
|
| [3] |
Wolff J A, Malone R W, Williams P, et al. Direct gene transfer into mouse muscle in vivo [J]. Science, 1990, 247(4949): 1465–1468.
|
| [4] |
刘君, 刘凤华, 吴海岚, 等. 全球冠状病毒疫苗研发态势分析 [J]. 中华实验和临床病毒学杂志, 2020, 34(4): 357–366. Liu J, Liu F H, Wu H L, et al. Analysis of global coronavirus vaccines development situation [J]. Chinese Journal of Experimental and Clinical Virology, 2020, 34(4): 357–366.
|
| [5] |
葛华, 蒋丽勇, 刘术, 等. COVID-19 DNA疫苗关键技术与产品 进展分析 [J]. 军事医学, 2020, 44(5): 349–353. Ge H, Jiang L Y, Liu S, et al. Progress in key technologies and products of COVID-19 DNA vaccine [J]. Military Medical Sciences, 2020, 44(5): 349–353.
|
| [6] |
葛华, 蒋丽勇, 刘术, 等. COVID-19 mRNA疫苗关键技术与产品 进展分析 [J]. 军事医学, 2020, 44(4): 264–268. Ge H, Jiang L Y, Liu S, et al. Progress in key technologies and products of COVID-19 mRNA vaccine [J]. Military Medical Sciences, 2020, 44(4): 264–268.
|
| [7] |
Xu S Q, Yang K P, Li R, et al. mRNA vaccine era mechanisms, drug platform and clinical prospection [J]. International Journal of Molecular Sciences, 2020, 21(18): 1–10.
|
| [8] |
胡瞬, 易有金, 胡涛, 等. mRNA疫苗的开发及临床研究进展 [J]. 中国生物工程杂志, 2019, 39(11): 105–112. Hu S, Yi Y J, Hu T, et al. Development and clinical progress of mRNA vaccine J]. China Biotechnology, 2019, 39(11): 105–112.
|
| [9] |
李学荣, 余新炳. 核酸疫苗及其免疫机制研究 [J]. 中国人兽共 患病杂志, 2000, 16(6): 82–86. Li X R, Yu X B. Study on the immune mechanism of nucleic acid vaccine [J]. Chinese Journal of Zoonoses, 2000, 16(6): 82–86.
|
| [10] |
Wolff J A, Ludtke J J, Acsadi G, et al. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle [J]. Human Molecular Genetics, 1992, 1(6): 363–369.
|
| [11] |
Coolen A L, Lacroix C, Mercier-Gouy P, et al. Poly (lactic acid) nanoparticles and cell-penetrating peptide potentiate mRNA-based vaccine expression in dendritic cells triggering their activation [J]. Biomaterials, 2019, 195: 23–37.
|
| [12] |
Williams R S, Johnston S A, Riedy M, et al. Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles [J]. Proceedings of the National Academy of Sciences of the United States of America, 1991, 88(7): 2726–2730.
|
| [13] |
Tang D C, DeVit M, Johnston S A. Genetic immunization is a simple method for eliciting an immune response [J]. Nature, 1992, 356(6365): 152–154.
|
| [14] |
Ulmer J B, Donnelly J J, Parker S E, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein [J]. Science, 1993, 259(5102): 1745–1749.
|
| [15] |
Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer [J]. Nature, 2017, 547(7662): 222–226..
|
| [16] |
范红, 于振行, 苏月, 等. 疫苗技术的研究进展和分析[J]. 中国新 药杂志, 2019, 28(14): 1665–1669. Fan H, Yu Z X, Su Y, et al. General analysis of the advances in vaccine technology [J]. Chinese Journal of New Drugs, 2019, 28(14): 1665–1669.
|
/
| 〈 |
|
〉 |
