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宋心雨1, 潘炜松1, 吴泰茹2, 潘家豪2, 吴川2, 李伟展3
收稿日期:
2025-03-26
修回日期:
2025-06-09
出版日期:
2025-06-12
通讯作者:
潘炜松
作者简介:
基金资助:
SONG Xinyu1, PAN Weisong1, WU Tairu2, PAN Jiahao2, WU Chuan2, Li Wai chin3
Received:
2025-03-26
Revised:
2025-06-09
Online:
2025-06-12
Contact:
PAN Weisong
摘要:
在当今全球公共卫生领域,疫苗作为预防和控制传染病的关键手段,其研发和生产技术的创新备受瞩目。植物源疫苗作为一种新兴的疫苗生产技术,凭借其独特的优势逐渐崭露头角。与传统疫苗生产方式相比,植物源疫苗具有显著优势,在分子生物学技术的加持下,能够在较短时间内实现大规模生产,有效应对传染病的大规模爆发。本文首先介绍了植物源疫苗的基本概念,阐述了植物源疫苗的发展历程,同时对植物源疫苗的不同分类方法进行了系统梳理,此外还探讨了植物源疫苗的表达平台和表达体系,比较了不同平台和体系如稳定表达和瞬时表达体系的优缺点,总结了提高疫苗效力和安全性的策略和优化方法,系统探讨了国内外植物源疫苗的开发进展。本文所综述的研究成果对于推动我国植物源疫苗的发展具有重要的理论和实践意义,为我国科研人员和相关企业提供了信息和参考。综上所述,植物源疫苗作为一种具有巨大潜力的新兴疫苗技术,有望在未来的公共卫生事业中发挥更加重要的作用。
中图分类号:
宋心雨, 潘炜松, 吴泰茹, 潘家豪, 吴川, 李伟展. 植物源疫苗研究进展[J]. 合成生物学, DOI: 10.12211/2096-8280.2025-029.
SONG Xinyu, PAN Weisong, WU Tairu, PAN Jiahao, WU Chuan, Li Wai chin. Research Progress in Plant-Derived Vaccines[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2025-029.
疫苗种类 | 目标抗原 | 受体植物 | 表达体系 | 参考文献 |
---|---|---|---|---|
病毒疫苗 | 人乙型肝炎病毒表面抗原(HBsAg)蛋白 | 番茄 | 稳定表达体系 | |
HIV中和人单克隆抗体2G 12 | 烟草 | 瞬时表达体系 | ||
SARS-CoV-2刺突蛋白的受体结合结构域 | 烟草 | 瞬时表达体系 | ||
人乳头状瘤病毒(HPV)疫苗 | 本氏烟草 | 瞬时表达体系 | ||
埃博拉病毒疫苗 | 烟草 | 瞬时表达系统 | ||
猪繁殖与呼吸综合征(PRRS)的亚单位疫苗 | 烟草 | 瞬时表达系统 | ||
禽流感病毒血凝素 | 马铃薯 | 瞬时表达系统 | ||
非洲猪瘟P30重组蛋白 | 本氏烟草 | 瞬时表达系统 | ||
诺瓦病毒VLP | 生菜 | 瞬时表达系统 | ||
埃博拉病毒和西尼罗河病毒的治疗性单克隆抗体mAb | 生菜 | 瞬时表达系统 | ||
HPV疫苗 | 生菜 | 瞬时表达系统 | ||
牛瘤病毒(BPV)病毒样颗粒 | 烟草 | 瞬时表达系统 | ||
人源轮状病毒VP7蛋白 | 花生 | 稳定表达系统 | ||
狂犬病病毒G蛋白 | 水稻 | 稳定表达系统 | ||
猪瘟E2融合蛋白 | 烟草 | 瞬时表达系统 | ||
癌胚抗原的单链Fv抗体 | 小麦 | 稳定表达系统 | ||
日本脑炎病毒(JEV)包膜蛋白(E) | 水稻胚乳 | 稳定表达系统 | ||
ErbB2酪氨酸激酶受体 | 烟草 | 瞬时表达系统 | ||
高尔基病 | A-L-艾杜糖苷酶 | 玉米种子胚乳 | 稳定表达系统 | |
细菌疫苗 | LTB-ST | 烟草 | 瞬时表达系统 | |
幽门螺旋杆菌ureB抗原 | 水稻胚乳 | 稳定表达系统 | ||
寄生虫疫苗 | 抗轮虫保护性抗原As16 | 水稻胚乳 | 稳定表达系统 | |
房尘螨(HDM)过敏源Der p 1 | 水稻胚乳 | 稳定表达系统 | ||
利什曼虫的前鞭毛体表面抗原(PSA) | 本氏烟草 | 瞬时表达系统 | ||
阿尔茨海默 | 淀粉样β肽Aβ 42 | 水稻胚乳 | 稳定表达系统 |
表1 一些已投入临床或动物实验的植物外源物质及其表达方式
Table 1 Plant-derived foreign substances that have been put into clinical or animal experiments and their expression methods
疫苗种类 | 目标抗原 | 受体植物 | 表达体系 | 参考文献 |
---|---|---|---|---|
病毒疫苗 | 人乙型肝炎病毒表面抗原(HBsAg)蛋白 | 番茄 | 稳定表达体系 | |
HIV中和人单克隆抗体2G 12 | 烟草 | 瞬时表达体系 | ||
SARS-CoV-2刺突蛋白的受体结合结构域 | 烟草 | 瞬时表达体系 | ||
人乳头状瘤病毒(HPV)疫苗 | 本氏烟草 | 瞬时表达体系 | ||
埃博拉病毒疫苗 | 烟草 | 瞬时表达系统 | ||
猪繁殖与呼吸综合征(PRRS)的亚单位疫苗 | 烟草 | 瞬时表达系统 | ||
禽流感病毒血凝素 | 马铃薯 | 瞬时表达系统 | ||
非洲猪瘟P30重组蛋白 | 本氏烟草 | 瞬时表达系统 | ||
诺瓦病毒VLP | 生菜 | 瞬时表达系统 | ||
埃博拉病毒和西尼罗河病毒的治疗性单克隆抗体mAb | 生菜 | 瞬时表达系统 | ||
HPV疫苗 | 生菜 | 瞬时表达系统 | ||
牛瘤病毒(BPV)病毒样颗粒 | 烟草 | 瞬时表达系统 | ||
人源轮状病毒VP7蛋白 | 花生 | 稳定表达系统 | ||
狂犬病病毒G蛋白 | 水稻 | 稳定表达系统 | ||
猪瘟E2融合蛋白 | 烟草 | 瞬时表达系统 | ||
癌胚抗原的单链Fv抗体 | 小麦 | 稳定表达系统 | ||
日本脑炎病毒(JEV)包膜蛋白(E) | 水稻胚乳 | 稳定表达系统 | ||
ErbB2酪氨酸激酶受体 | 烟草 | 瞬时表达系统 | ||
高尔基病 | A-L-艾杜糖苷酶 | 玉米种子胚乳 | 稳定表达系统 | |
细菌疫苗 | LTB-ST | 烟草 | 瞬时表达系统 | |
幽门螺旋杆菌ureB抗原 | 水稻胚乳 | 稳定表达系统 | ||
寄生虫疫苗 | 抗轮虫保护性抗原As16 | 水稻胚乳 | 稳定表达系统 | |
房尘螨(HDM)过敏源Der p 1 | 水稻胚乳 | 稳定表达系统 | ||
利什曼虫的前鞭毛体表面抗原(PSA) | 本氏烟草 | 瞬时表达系统 | ||
阿尔茨海默 | 淀粉样β肽Aβ 42 | 水稻胚乳 | 稳定表达系统 |
抗原 | 表达系统 | 宿主 | 参考文献 |
---|---|---|---|
猪O型口蹄疫病毒(FMDV)抗原表位融合结构蛋白VP1 | 瞬时表达 | 本氏烟草 | |
呼吸道合胞病毒(RSV)F蛋白 | 瞬时表达 | 本氏烟草 | |
霍乱毒素B亚基(CTB) | 瞬时表达 | 本氏烟草 | |
中东呼吸综合征冠状病毒刺突蛋白S1亚基抗原 | 瞬时表达 | 本氏烟草 |
表2 植物来源的一些抗原实例
Table 2 Plant-derived antigen examples
抗原 | 表达系统 | 宿主 | 参考文献 |
---|---|---|---|
猪O型口蹄疫病毒(FMDV)抗原表位融合结构蛋白VP1 | 瞬时表达 | 本氏烟草 | |
呼吸道合胞病毒(RSV)F蛋白 | 瞬时表达 | 本氏烟草 | |
霍乱毒素B亚基(CTB) | 瞬时表达 | 本氏烟草 | |
中东呼吸综合征冠状病毒刺突蛋白S1亚基抗原 | 瞬时表达 | 本氏烟草 |
抗原 | 表达系统 | 植物宿主 | 参考文献 |
---|---|---|---|
Influenza A H5N1 HA | 用质体蓝素表达载体瞬时表达 | 本氏烟草N. benthamiana | [ |
HBsAg L protein | 稳定的转基因植物 | 烟草Tobacco | [ |
Dengue-3 capsid, prM/M and E | 稳定的转质体叶绿体表达 | 莴苣Lettuce | [ |
HBsAg VLP displaying HIV-1 ENV and GAG epitopes | 稳定的转基因植物 | 番茄tomato | [ |
HBsAg VLP displaying HIV-1 polyepitope | 稳定的转基因植物 | 烟草Tobacco 拟南芥Arabidopsis | [ |
HBsAg VLP displaying HBV preS1 epitope | 稳定的转基因植物 | 水稻Rice | [ |
HBsAg VLP displaying full- length GFP | 用非病毒载体瞬时表达 | 本氏烟草N. benthamiana | [ |
HIV-1Gag VLP displaying gp41 | MagnICON“解构”病毒载体的瞬时表达 | 本氏烟草N. benthamiana | [ |
表3 植物来源的一些包膜VLP的实例[15]
Table 3 Examples of some plant-derived enveloped VLPs
抗原 | 表达系统 | 植物宿主 | 参考文献 |
---|---|---|---|
Influenza A H5N1 HA | 用质体蓝素表达载体瞬时表达 | 本氏烟草N. benthamiana | [ |
HBsAg L protein | 稳定的转基因植物 | 烟草Tobacco | [ |
Dengue-3 capsid, prM/M and E | 稳定的转质体叶绿体表达 | 莴苣Lettuce | [ |
HBsAg VLP displaying HIV-1 ENV and GAG epitopes | 稳定的转基因植物 | 番茄tomato | [ |
HBsAg VLP displaying HIV-1 polyepitope | 稳定的转基因植物 | 烟草Tobacco 拟南芥Arabidopsis | [ |
HBsAg VLP displaying HBV preS1 epitope | 稳定的转基因植物 | 水稻Rice | [ |
HBsAg VLP displaying full- length GFP | 用非病毒载体瞬时表达 | 本氏烟草N. benthamiana | [ |
HIV-1Gag VLP displaying gp41 | MagnICON“解构”病毒载体的瞬时表达 | 本氏烟草N. benthamiana | [ |
图1 植物源疫苗的生产流程[5](基因设计构建质粒载体,将载体通过适当的方法导入宿主植物,让目的基因在宿主植物体内表达,收集表达目标蛋白的植物组织,研磨后提取蛋白,纯化后得到产品。)
Fig. 1 The production process of plant-derived vaccines(Design and construct the plasmid vector for the gene. Introduce the vector into the host plant using appropriate methods. Allow the target gene to be expressed within the host plant. Collect the plant tissues that express the target protein. Grind the tissues to extract the protein. Purify the protein to obtain the final product.)
图2 植物源疫苗的优化(植物源疫苗的优化可以通过优化载体,优化目标抗原的选择,优化蛋白质修饰,让目的基因与蛋白酶抑制剂基因和沉默抑制基因共表达,优化纯化过程来达成。图中P19蛋白基因共表达参考Jiexue等人的研究。本图由Figdraw绘制。)
Fig. 2 Optimization of Plant-derived Vaccines(The optimization of plant-derived vaccines can be achieved through the optimization of vectors, the selection of target antigens, the modification of proteins, co-expression of the target gene with protease inhibitor genes and silencing suppressor genes, and the optimization of the purification process. The co-expression of the P19 protein gene in the figure refers to the study by Jiexue et al. By Figdraw.)
植物蛋白酶抑制剂PI | 参考文献 |
---|---|
半胱氨酸蛋白酶抑制剂PhyCys家族 | |
丝氨酸蛋白酶抑制剂家族 | |
α-淀粉酶/胰蛋白酶抑制剂家族 | |
南瓜胰蛋白酶抑制剂家族 | |
芥菜胰蛋白酶抑制剂家族 | |
天冬氨酸蛋白酶抑制剂家族 | |
金属羧肽酶抑制剂家族 | |
Bowman-Birk Ser蛋白酶抑制剂 | |
烟草丝氨酸蛋白酶抑制剂II基因的胰蛋白酶(C1)和胰凝乳蛋白酶(T1)抑制域 | |
水稻半胱氨酸蛋白酶抑制剂oryzacystatin-I | |
番茄组织蛋白酶D抑制剂(SlCDI) | |
番茄半胱氨酸蛋白酶抑制剂SlCYS 8 | |
CaPR 4c | |
NbPot1 | |
HsTIMP靶向基质金属蛋白酶 |
表 4 一些常用植物蛋白酶抑制剂
Table 4 Some commonly used plant protease inhibitors
植物蛋白酶抑制剂PI | 参考文献 |
---|---|
半胱氨酸蛋白酶抑制剂PhyCys家族 | |
丝氨酸蛋白酶抑制剂家族 | |
α-淀粉酶/胰蛋白酶抑制剂家族 | |
南瓜胰蛋白酶抑制剂家族 | |
芥菜胰蛋白酶抑制剂家族 | |
天冬氨酸蛋白酶抑制剂家族 | |
金属羧肽酶抑制剂家族 | |
Bowman-Birk Ser蛋白酶抑制剂 | |
烟草丝氨酸蛋白酶抑制剂II基因的胰蛋白酶(C1)和胰凝乳蛋白酶(T1)抑制域 | |
水稻半胱氨酸蛋白酶抑制剂oryzacystatin-I | |
番茄组织蛋白酶D抑制剂(SlCDI) | |
番茄半胱氨酸蛋白酶抑制剂SlCYS 8 | |
CaPR 4c | |
NbPot1 | |
HsTIMP靶向基质金属蛋白酶 |
图3 P19蛋白作用原理(侵入植物体的病毒RNA会组装成双链shRNA,被Dicer酶切成21-23bp的siRNA,与RISC组合成siRNA-RISC复合体,并结合至同源的mRNA上使其裂解。而当P19蛋白被表达后,它会组装成二聚体结合siRNA,使siRNA无法结合RISC,从而使沉默过程无法进行。本图由Figdraw绘制。)
Fig. 3 The Mechanism of Action of P19 Protein(The viral RNA that invades the plant body is assembled into double-stranded shRNA, which is cut into 21-23 base pair siRNAs by the Dicer enzyme. These siRNAs form a siRNA-RISC complex and bind to the homologous mRNA, causing it to be cleaved. However, when the P19 protein is expressed, it assembles into a dimer that binds to the siRNA, preventing the siRNA from binding to RISC, and thus the silencing process cannot proceed. By Figdraw.)
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