合成生物学 ›› 2023, Vol. 4 ›› Issue (2): 333-346.DOI: 10.12211/2096-8280.2022-064
申赵铃, 吴艳玲, 应天雷
收稿日期:
2022-11-21
修回日期:
2022-12-29
出版日期:
2023-04-30
发布日期:
2023-04-27
通讯作者:
应天雷
作者简介:
基金资助:
Zhaoling SHEN, Yanling WU, Tianlei YING
Received:
2022-11-21
Revised:
2022-12-29
Online:
2023-04-30
Published:
2023-04-27
Contact:
Tianlei YING
摘要:
病毒所致的传染性疾病严重危害公共卫生安全,给全球人类健康与经济发展带来了巨大的威胁。疫苗是防治传染性疾病传播的一个关键且有效的手段,包括全病毒疫苗、亚单位疫苗、核酸疫苗等。然而,现有的疫苗开发策略面临研发周期、有效性、安全性等系列问题,是当今应对新发传染病的难点和痛点。利用合成生物学技术,比如密码子优化技术、可基因编码点击化学技术、生物偶联技术等,可以克服以上问题,在短时间内研发出安全且高效的病毒合成疫苗,因此合成生物学技术在病毒合成疫苗研发中的应用越来越广泛。本文总结了传统病毒疫苗的现状与应用,进而阐述了合成生物学技术在病毒疫苗研发中的应用与优势,并提出了病毒合成疫苗将要面临的挑战,为设计下一代新型病毒疫苗提供思路和方法。
中图分类号:
申赵铃, 吴艳玲, 应天雷. 合成生物学与病毒疫苗研发[J]. 合成生物学, 2023, 4(2): 333-346.
Zhaoling SHEN, Yanling WU, Tianlei YING. Synthetic biology and viral vaccine development[J]. Synthetic Biology Journal, 2023, 4(2): 333-346.
图1 病毒性流行病及相关病原体(近40年)
Fig. 1 Outbreaks of deadly viral epidemics caused by human immunodeficiency virus, SARS coronavirus, influenza A virus H1N1, MERS-CoV, Ebola virus and SARS-CoV-2, respectively, within the past four decades.
类型 | 优势 | 局限性 | 应用 |
---|---|---|---|
灭活病毒疫苗 inactivated vaccines | 相对安全 热稳定性较好 免疫功能低下者和孕妇可考虑 | 免疫原性有限 需要佐剂 持续性短 诱导疾病进展 | 狂犬病 日本脑炎 甲型肝炎 |
减毒活病毒疫苗 live attenuated virus vaccines | 模拟自然感染 同时诱导先天性和适应性免疫反应 1~2次剂量后可获得终身免疫 | 热稳定性较差 免疫功能低下者禁用 有逆转为野生型病毒的可能性 | 麻疹 腮腺炎 流感 脊髓灰质炎 |
亚单位疫苗 subunit vaccines | 无传染性 高稳定性 高安全性 | 免疫原性有限 需要佐剂 | 乙型肝炎 新冠肺炎 |
DNA疫苗 DNA vaccines | 热稳定性好 刺激先天免疫反应 诱导T细胞和B细胞免疫反应 | 潜在基因组整合风险 免疫原性较弱 需要电穿孔等方式递送 | 埃博拉出血热 |
RNA疫苗 RNA vaccines | 无传染性 不存在潜在基因组整合风险 | 稳定性差 易降解性 过度产生炎性反应 | 新冠肺炎 |
病毒载体疫苗 viral vector vaccines | 应用广泛 同时诱导体液和细胞免疫反应 研发周期短 | 可能致病性 | 埃博拉出血热 |
表1 各类病毒疫苗的优缺点及其应用
Table 1 Advantages,disadvantages and the applications of different kinds of vaccines
类型 | 优势 | 局限性 | 应用 |
---|---|---|---|
灭活病毒疫苗 inactivated vaccines | 相对安全 热稳定性较好 免疫功能低下者和孕妇可考虑 | 免疫原性有限 需要佐剂 持续性短 诱导疾病进展 | 狂犬病 日本脑炎 甲型肝炎 |
减毒活病毒疫苗 live attenuated virus vaccines | 模拟自然感染 同时诱导先天性和适应性免疫反应 1~2次剂量后可获得终身免疫 | 热稳定性较差 免疫功能低下者禁用 有逆转为野生型病毒的可能性 | 麻疹 腮腺炎 流感 脊髓灰质炎 |
亚单位疫苗 subunit vaccines | 无传染性 高稳定性 高安全性 | 免疫原性有限 需要佐剂 | 乙型肝炎 新冠肺炎 |
DNA疫苗 DNA vaccines | 热稳定性好 刺激先天免疫反应 诱导T细胞和B细胞免疫反应 | 潜在基因组整合风险 免疫原性较弱 需要电穿孔等方式递送 | 埃博拉出血热 |
RNA疫苗 RNA vaccines | 无传染性 不存在潜在基因组整合风险 | 稳定性差 易降解性 过度产生炎性反应 | 新冠肺炎 |
病毒载体疫苗 viral vector vaccines | 应用广泛 同时诱导体液和细胞免疫反应 研发周期短 | 可能致病性 | 埃博拉出血热 |
图2 合成生物技术在病毒疫苗中的应用(a) Codon optimization/deoptimization: The expression level of viral protein can be increased through codon optimization, but codon deoptimization can result in the production of live attenuated vaccines. (b) Nucleic acid vaccines: mRNA is modified with intact 5′ cap structure and 3′ polytail structure for stable expression, and microcyclic DNA is inserted into viral protein coding sequences and exogenous promoter sequences through restriction digestion sites to construct recombinant plasmids. (c) Viral vectors vaccines:viral protein coding sequences are inserted into viral vector sequences to generate recombinant viral vectors. (d) Virus-like particle (VLP) vaccines: multi-antigen VLP vaccines are developed based on GECC generation, and VLP vaccines include immunomodulators, and ring structures to accommodate antigen peptides for recognition
Fig. 2 Synthetic biology technologies for developing viral vaccines
图3 合成生物技术在病毒疫苗中的应用与优势总结(Synthetic vaccines include genomic codon-optimized vaccines, synthetic genome-based nucleic acid vaccines, viral vector-based vaccines, and virus-like particle vaccines, which can be produced on large-scale production in recombinant yeasts to shorten time for vaccine development with advantages in enhancing immunogenicity, and broadening spectrum, and improving safety and efficacy)
Fig. 3 Applications and advantges of synthetic biotechnologies in the development of synthetic vaccines
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