Synthetic Biology Journal ›› 2024, Vol. 5 ›› Issue (2): 369-384.DOI: 10.12211/2096-8280.2023-088
• Invited Review • Previous Articles Next Articles
Weifeng YUAN, Yongliang ZHAO, Zhixuan WU, Ke XU
Received:
2023-11-28
Revised:
2024-02-18
Online:
2024-04-28
Published:
2024-04-30
Contact:
Ke XU
袁为锋, 赵永亮, 吴芷萱, 徐可
通讯作者:
徐可
作者简介:
基金资助:
CLC Number:
Weifeng YUAN, Yongliang ZHAO, Zhixuan WU, Ke XU. Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines[J]. Synthetic Biology Journal, 2024, 5(2): 369-384.
袁为锋, 赵永亮, 吴芷萱, 徐可. 合成生物学在新冠病毒广谱疫苗研发中的应用[J]. 合成生物学, 2024, 5(2): 369-384.
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疫苗类型 | 产品名 | 关键组分或技术 | 保护率或临床阶段 | 研发团队或机构 |
---|---|---|---|---|
灭活疫苗 | CoronaVac | CZ02株 | 50.4%[ | 北京科兴中维生物 |
BBIBP-CorV | HB02株 | 78.1%[ | 北京生物制品研究所 | |
WIBP | WIV04株 | 72.8%[ | 武汉生物制品研究所 | |
BBV152 | NIV-2020-770株 | 77.8%[ | Bharat Biotech | |
QazVac | Wuhan-Hu-1株 | 90%[ | Kazakhstan RIBSP | |
纳米颗粒疫苗 | I53-50 | RBD | Ⅲ期(原始株) | 华盛顿大学[ |
铁蛋白 | S | Ⅰ期(原始株) | 斯坦福大学[ | |
SC003-mi3 | RBD | Ⅱ/Ⅲ期(原始株) | 牛津大学[ | |
铁蛋白 | RBD | 临床前(突变株) | 中山大学[ | |
亚单位疫苗 | NVXCoV2373 | Matrix-M™佐剂 | 89.7%[ | Novavax |
COVAX-19 | Advax-CpG55.2™佐剂 | 63.55%[ | Vaxine Pty Ltd | |
SCB-2019 | CpG 1018、铝佐剂 | 67%[ | 三叶草 | |
ZF2001 | 氢氧化铝佐剂 | 75.7%[ | 中国科学院微生物研究所 | |
威克欣 | MF59样佐剂 | 未公布[ | 威斯克生物 | |
SCTV01C | 水包油佐剂 | 未公布[ | 神州细胞 | |
MVC-COV1901 | CpG1018、明矾佐剂 | 未公布[ | Medigen Vaccine Biologics | |
Soberana | 明矾、B群脑膜炎奈瑟氏菌外膜囊泡 | 未公布[ | 古巴芬利疫苗研究所 | |
病毒载体疫苗 | Ad26.COV2.S | Ad26腺病毒载体 | 66.1%[ | Janssen |
Sputnik V | rAd26和rAd5腺病毒载体 | 91.6%[ | Gamaleya Center | |
Ad5-nCoV | Ad5腺病毒载体 | 57.5%[ | 康希诺生物、军事医学科学院 | |
AZD1222 | ChAdOx1腺病毒载体 | 76%[ | 阿斯利康、牛津大学 | |
dNS1-RBD | dNS1流感病毒载体 | 100%[ | 厦门大学、香港大学、万泰生物 | |
核酸疫苗 | BNT162b2 | mRNA疫苗 | 95%[ | Pfizer Inc. |
mRNA-1273 | mRNA疫苗 | 94.1%[ | Moderna | |
ARCoV | mRNA疫苗 | 83.75%[ | 艾博生物 | |
ZyCov-D | DNA疫苗 | 67%[ | Zydus Cadila |
Table 1 Research progress in SARS-CoV-2 vaccines
疫苗类型 | 产品名 | 关键组分或技术 | 保护率或临床阶段 | 研发团队或机构 |
---|---|---|---|---|
灭活疫苗 | CoronaVac | CZ02株 | 50.4%[ | 北京科兴中维生物 |
BBIBP-CorV | HB02株 | 78.1%[ | 北京生物制品研究所 | |
WIBP | WIV04株 | 72.8%[ | 武汉生物制品研究所 | |
BBV152 | NIV-2020-770株 | 77.8%[ | Bharat Biotech | |
QazVac | Wuhan-Hu-1株 | 90%[ | Kazakhstan RIBSP | |
纳米颗粒疫苗 | I53-50 | RBD | Ⅲ期(原始株) | 华盛顿大学[ |
铁蛋白 | S | Ⅰ期(原始株) | 斯坦福大学[ | |
SC003-mi3 | RBD | Ⅱ/Ⅲ期(原始株) | 牛津大学[ | |
铁蛋白 | RBD | 临床前(突变株) | 中山大学[ | |
亚单位疫苗 | NVXCoV2373 | Matrix-M™佐剂 | 89.7%[ | Novavax |
COVAX-19 | Advax-CpG55.2™佐剂 | 63.55%[ | Vaxine Pty Ltd | |
SCB-2019 | CpG 1018、铝佐剂 | 67%[ | 三叶草 | |
ZF2001 | 氢氧化铝佐剂 | 75.7%[ | 中国科学院微生物研究所 | |
威克欣 | MF59样佐剂 | 未公布[ | 威斯克生物 | |
SCTV01C | 水包油佐剂 | 未公布[ | 神州细胞 | |
MVC-COV1901 | CpG1018、明矾佐剂 | 未公布[ | Medigen Vaccine Biologics | |
Soberana | 明矾、B群脑膜炎奈瑟氏菌外膜囊泡 | 未公布[ | 古巴芬利疫苗研究所 | |
病毒载体疫苗 | Ad26.COV2.S | Ad26腺病毒载体 | 66.1%[ | Janssen |
Sputnik V | rAd26和rAd5腺病毒载体 | 91.6%[ | Gamaleya Center | |
Ad5-nCoV | Ad5腺病毒载体 | 57.5%[ | 康希诺生物、军事医学科学院 | |
AZD1222 | ChAdOx1腺病毒载体 | 76%[ | 阿斯利康、牛津大学 | |
dNS1-RBD | dNS1流感病毒载体 | 100%[ | 厦门大学、香港大学、万泰生物 | |
核酸疫苗 | BNT162b2 | mRNA疫苗 | 95%[ | Pfizer Inc. |
mRNA-1273 | mRNA疫苗 | 94.1%[ | Moderna | |
ARCoV | mRNA疫苗 | 83.75%[ | 艾博生物 | |
ZyCov-D | DNA疫苗 | 67%[ | Zydus Cadila |
疫苗产品 | 疫苗类型 | 抗原 | 临床阶段 | 研发机构 |
---|---|---|---|---|
SpFN[ | 亚单位 | 多种突变株的S蛋白 | Ⅰ | 美国沃尔特-里德陆军研究所 |
RBD-scNP[ | 亚单位 | 多种突变株的RBD蛋白 | 临床前 | 杜克大学 |
复必泰[ | mRNA | WT和BA.4/5的S蛋白 | Ⅰ | 复星医药 |
RBD-sc[ | 亚单位 | 不同突变株的RBD二聚体 | 临床前 | 中国科学院微生物研究所 |
V-01D-351[ | 亚单位 | Beta和Delta株的RBD二聚体 | Ⅰ | 丽珠集团 |
SCTV01C[ | 亚单位 | Alpha和Beta株的S蛋白 | Ⅲ | 神州细胞 |
SCTV01E[ | 亚单位 | Alpha、Beta、Delta和Omicron株的S蛋白 | Ⅲ | 神州细胞 |
Table 2 Research progress in developing the SARS-CoV-2 vaccine with the Mosaic strategy
疫苗产品 | 疫苗类型 | 抗原 | 临床阶段 | 研发机构 |
---|---|---|---|---|
SpFN[ | 亚单位 | 多种突变株的S蛋白 | Ⅰ | 美国沃尔特-里德陆军研究所 |
RBD-scNP[ | 亚单位 | 多种突变株的RBD蛋白 | 临床前 | 杜克大学 |
复必泰[ | mRNA | WT和BA.4/5的S蛋白 | Ⅰ | 复星医药 |
RBD-sc[ | 亚单位 | 不同突变株的RBD二聚体 | 临床前 | 中国科学院微生物研究所 |
V-01D-351[ | 亚单位 | Beta和Delta株的RBD二聚体 | Ⅰ | 丽珠集团 |
SCTV01C[ | 亚单位 | Alpha和Beta株的S蛋白 | Ⅲ | 神州细胞 |
SCTV01E[ | 亚单位 | Alpha、Beta、Delta和Omicron株的S蛋白 | Ⅲ | 神州细胞 |
Fig. 2 Schematic diagram for engineering conserved epitopes HR1 and HR2 to develop broad-spectrum vaccine antigens(Membrane fusion mediated by the SARS-CoV-2 S2 subunit. Initially, the standing RBD engages with ACE2, and subsequently, the S1 subunit dissociates from S2, followed by the exposure of the S2 site and the cleavage of S2 by the host proteases. HR1 undergoes a “jack-knife” refolding change to allow the insertion of FP into the host cell membrane. The folding back of the extended SH-HR2 element packs against the long central CH-HR1 coiled-coil, inducing the binding of SH onto the outer region of CH and HR2 to the HR1 groove. Subsequently, membrane fusion occurs between the viral particles and host cells.)
疫苗产品 | 疫苗类型 | 抗原 | 临床阶段 | 研发机构 |
---|---|---|---|---|
HR121[ | 亚单位 | HR1-HR2-HR1串联 | 临床前 | 中国科学院昆明动物研究所 |
HR1LS[ | 亚单位 | HR1-CH-SH串联 | 临床前 | 复旦大学 |
MigVax-101[ | 亚单位 | RBD和N蛋白 | 临床前 | MigVax |
STFK1628x/y[ | 亚单位 | B.1.620-NTD和Gamma-RBD-S2 | 临床前 | 厦门大学 |
hAd5 S-Fusion+N-ETSD[ | 病毒载体 | S和N蛋白 | Ⅱ | ImmunityBio |
Table 3 Research progress in vaccines against the conserved epitope of SARS-CoV-2
疫苗产品 | 疫苗类型 | 抗原 | 临床阶段 | 研发机构 |
---|---|---|---|---|
HR121[ | 亚单位 | HR1-HR2-HR1串联 | 临床前 | 中国科学院昆明动物研究所 |
HR1LS[ | 亚单位 | HR1-CH-SH串联 | 临床前 | 复旦大学 |
MigVax-101[ | 亚单位 | RBD和N蛋白 | 临床前 | MigVax |
STFK1628x/y[ | 亚单位 | B.1.620-NTD和Gamma-RBD-S2 | 临床前 | 厦门大学 |
hAd5 S-Fusion+N-ETSD[ | 病毒载体 | S和N蛋白 | Ⅱ | ImmunityBio |
Fig. 4 Schematic diagram of strategy for designing consensus sequences[62](Taking the SARS-CoV-2 consensus sequence Span as an example. ① Establishing the whole sequences library; ② Evolutionary calculations of the viruses; ③ Constructing an evolutionary tree for the viral strains to obtain representative ones for each branch; ④ Utilizing representative strains to calculate the consensus sequences, and refining and optimizing them by incorporating back into the database; ⑤ Obtaining the consensus sequences located at the evolutionary center.)
疫苗产品 | 疫苗类型 | 抗原 | 佐剂 | 临床阶段 | 研发机构 |
---|---|---|---|---|---|
β-CoV-B[ | 亚单位 | WT-RBD | CF501 | 临床前 | 复旦大学 |
NVX-CoV2373[ | 亚单位 | S | Matrix-M | 已上市 | Novavax |
VLA2001[ | 灭活疫苗 | WT毒株 | 铝佐剂和CpG 1018 | 已上市 | Valneva SE |
YS-SC2-010[ | 亚单位 | WT-S | 皮卡佐剂 | Ⅰ | 依生生物 |
Table 4 Research progress of the SARS-CoV-2 vaccines developed based on novel adjuvant strategies
疫苗产品 | 疫苗类型 | 抗原 | 佐剂 | 临床阶段 | 研发机构 |
---|---|---|---|---|---|
β-CoV-B[ | 亚单位 | WT-RBD | CF501 | 临床前 | 复旦大学 |
NVX-CoV2373[ | 亚单位 | S | Matrix-M | 已上市 | Novavax |
VLA2001[ | 灭活疫苗 | WT毒株 | 铝佐剂和CpG 1018 | 已上市 | Valneva SE |
YS-SC2-010[ | 亚单位 | WT-S | 皮卡佐剂 | Ⅰ | 依生生物 |
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