中国畜牧兽医 ›› 2026, Vol. 53 ›› Issue (1): 81-93.doi: 10.16431/j.cnki.1671-7236.2026.01.008
郭双霖1,2(
), 郝飞2, 刘永杰1, 秦浩然2,3, 陈蓉2, 马孙婷2, 冯志新2, 谢星1,2,3(
)
收稿日期:2025-04-15
出版日期:2026-01-05
发布日期:2025-12-26
通讯作者:
谢星
E-mail:gsl5050@163.com;yzxx1989@163.com
作者简介:郭双霖,E-mail: gsl5050@163.com
基金资助:
GUO Shuanglin1,2(
), HAO Fei2, LIU Yongjie1, QIN Haoran2,3, CHEN Rong2, MA Sunting2, FENG Zhixin2, XIE Xing1,2,3(
)
Received:2025-04-15
Online:2026-01-05
Published:2025-12-26
Contact:
XIE Xing
E-mail:gsl5050@163.com;yzxx1989@163.com
摘要:
重组活载体疫苗利用病原体作为载体递送目标抗原,具有免疫效果强、生产成本低、免疫策略灵活等优势,在传染病防控和肿瘤治疗等领域展现出广阔前景。笔者系统综述了细菌和病毒活载体疫苗的研究进展,重点分析了其抗原表达特性、适用动物模型及免疫效果。在细菌载体方面,卡介苗通过基因改造表达结核分枝杆菌抗原或免疫调节因子,可显著提升免疫效果;沙门菌载体因其口服接种便利性在黏膜免疫和癌症治疗中表现突出;乳酸菌作为载体可诱导黏膜和全身免疫。此外,大肠杆菌、枯草芽孢杆菌等也在抗感染和抗肿瘤疫苗研发中取得进展。病毒载体方面,腺病毒因其高效的转导能力,已成功用于新型冠状病毒肺炎和猪流感疫苗开发;痘病毒因其可容纳大片段外源基因,适用于多价疫苗设计;疱疹病毒宿主范围有限,安全性高,在表达口蹄疫病毒和流感病毒抗原时表现出良好的免疫原性;新城疫病毒和猪繁殖与呼吸障碍综合征病毒等RNA病毒载体因其独特的复制特性成为多病原联苗的理想平台。此外,肠道病毒载体在神经系统疾病治疗中也显示出潜力。尽管活载体疫苗已取得显著成果,但其免疫效率提升、安全性优化及规模化生产仍是未来研究重点。本综述为活载体疫苗的进一步开发和临床应用提供了重要参考。
中图分类号:
郭双霖, 郝飞, 刘永杰, 秦浩然, 陈蓉, 马孙婷, 冯志新, 谢星. 重组活载体疫苗研究进展[J]. 中国畜牧兽医, 2026, 53(1): 81-93.
GUO Shuanglin, HAO Fei, LIU Yongjie, QIN Haoran, CHEN Rong, MA Sunting, FENG Zhixin, XIE Xing. Advances in Recombinant Live Vector Vaccine[J]. China Animal Husbandry & Veterinary Medicine, 2026, 53(1): 81-93.
表1
载体疫苗研究进展情况"
载体类型 Vector types | 载体 Vectors | 疫苗/载体名称 Vaccine/vector name | 抗原 Antigen | 试验动物 Animal model | 是否攻毒 Challenge or not | 免疫效果 Immunization efficacy | 参考文献 References |
|---|---|---|---|---|---|---|---|
细菌载体 Bacterial vector | 卡介苗 | Δure hly+ rBCG(VPM1002) | 单核细胞增生李斯特菌的膜穿孔溶血素(Hly) | BALB/c 小鼠 | 是 | 肺内结核负担显著降低,高剂量攻毒疫苗组存活时间更长 | Grode等[ |
| rBCG30 | 表达结核分枝杆菌30 ku主要分泌蛋白 | 豚鼠(Hartley strain) | 是 | 肝脏和脾脏中的结节降为原来的约1/10 | Horwitz等[ | ||
rBCG::A rBCG::B rBCG::AB | 分别表达结核分枝杆菌Ag85A、Ag85B及Ag85A和Ag85B | C57BL/6 小鼠 | 是 | 双抗原重组疫苗对肺脏具有最强的短期和长期保护作用 | Wang等[ | ||
| IL-2-BZLF1-rBCG | 人IL-2和EBV BZLF1 | 否 | Yu等[ | ||||
| 沙门菌 | SL 7207 pYA:120 | HIV-1 gp120 | 否 | Fouts[ | |||
| — | 柔嫩艾美耳球虫抗原 | 否 | Pogonka等[ | ||||
| PsifB::sseJ | 表达coSVN(生存素) | CT26小鼠 | 否(治疗性接种) | 通过CD8+ T细胞产生cxcr3依赖性肿瘤浸润,触发强效抗肿瘤活性 | Xu等[ | ||
| 乳酸菌 | L.casei-OMP16-PEDVS | 表达PEDVS蛋白和流产布鲁氏菌OMP16蛋白 | 否 | Li等[ | |||
L. plantarum NC8-Tsgal | 表达旋毛虫半乳糖凝集素 | BALB/c 小鼠 | 是 | 肠道成虫与肌肉幼虫减少 | Xu等[ | ||
pSIP409-p32-HA2/NC8 pNZ8149-HA2/NZ3900 | 表达 AIV HA2蛋白 | 鸡 | 是 | 2组重组乳杆菌均能显著减少H9N2亚型AIV排毒 | Liu等[ | ||
| G型产气梭菌的主要毒素抗原表位CA、CN | 鸡 | 是 | 血清中特异性IgG含量上升,肠道病变减轻 | 王登潮[ | |||
大肠 杆菌 | rMAP62-54c/BL21 | 表面展示副结核分枝杆菌重组蛋白 | BALB/c 小鼠 | 是 | 脏器无明显病变,体重维持稳定 | 丁仕豪等[ | |
| E.coli LLO/OVA | 表达单核细胞增生李斯特菌溶血素O和卵清蛋白 | B16 OVA黑色素瘤 小鼠 | 是 | 有效预防B16 OVA黑色素小鼠的肿瘤肺转移 | Xu等[ | ||
| EcN-5M2e | 表达5M2e抗原(H1N1、H2N2、H3N2、H5N1和H7N9的M2e序列串联) | BALB/c 小鼠 | 是 | 与PBS组的小鼠相比,EcN-5M2e组的所有小鼠在流感病毒攻击后均存活 | Huang等[ | ||
| EcN-MPER | 插入HIV-1 MPER序列 | 否 | Ninyio等[ | ||||
病毒载体 Viral vector | 腺病毒 | Ad5-HA-14.2 Ad5-NP-13.4 | 表达H3N2亚型SIV血凝素或核蛋白的人腺病毒5型 | 猪 | 是 | 2种混合重组病毒的免疫组得到完全保护 | Wesley等[ |
| rPAV-gp55 | 插入CSFV Weybridge株gp55 (E2)基因 | 猪 | 是 | 起到完全保护作用,无临床症状 | Hammond等[ | ||
| 痘病毒 | FMDV P12A3C和PRRV HF蛋白 | 否 | Zhao等[ | ||||
| 表达了SARS-CoV-2突刺基因 | 否 | Awasthi 等[ | |||||
| T10-F10 | 表达CMV抗原IE1、IE2、pp65 | Yll-Pico 等[ | |||||
| 疱疹病毒 | 表达狂犬病毒G蛋白的重组CHV | 否 | Xuan等[ | ||||
| PRV TK-/gE-/P1-2A-VP2 | 共表达FMDV前体蛋白P1-2A和PPV VP2蛋白的PRV | BALB/c 小鼠 | 是 | 只验证对PRV的保护作用 | Hong等[ | ||
| 表达甲型H1N1亚型流感病毒的HA重组PRV | 猪 | 是 | 单次鼻内免疫可保护猪免受H1N1亚型流感病毒攻击,但病毒的复制并没有被完全抑制 | Klingbeil 等[ | |||
| PrV-BaMI-synN1 | 表达N1神经氨酸酶的PrV-Ba重组PRV | 猪 | 是 | 疫苗接种可显著抑制攻击病毒复制 | Klingbeil 等[ | ||
| rHVT-VP2 | 插入IBDV(G2d)的VP2基因 | 鸡 | 是 | rHVT-VP2组保护指数达100%,且未检测到IBDV | Zhang等[ | ||
| NDV | rNDV/B1-HA | 表达流感病毒血凝素的感染性重组病毒 | BALB/c 小鼠 | 是 | 小鼠免疫后致死剂量的流感病毒攻毒,小鼠存活 | Nakaya等[ | |
| HPIV3血凝素-神经氨酸酶蛋白 | 否 | Bukreyev 等[ | |||||
| rLaSota/VP2 | 表达IBDV VP2 | 鸡 | 是 | 接种疫苗产生了针对NDV和IBDV的抗体应答,并对NDV和IBDV提供了90%的保护 | Huang等[ | ||
| PRRSV | rPRRSV-E2 | 表达CSFV E2蛋白 | 猪 | 是 | 免疫后的猪在20和24周对HP-PRRSV或CSFV的攻击有很好的保护作用 | Gao等[ | |
| PCV2衣壳蛋白 | 否 | Pei等[ | |||||
| rPRRSV-mCherry-EGFP | 表达2种外源性蛋白(EGFP和mCherry) | 否 | Li等[ | ||||
肠道 病毒 | BDNF成熟肽的核苷酸序列插入脊髓灰质炎病毒 | 否 | Jia等[ | ||||
CVB3/0-mil4 /47 CVB3-pl2-mil4/46 | 小鼠IL-4 | 否 | Chapman等[ | ||||
| FMDV衣壳蛋白(VP1)表位 | 否 | Chu等[ | |||||
rHY12-3A-2-HA rHY12-3A-3-HA rHY12-3A-9-HA | 重组HY12 BEV的全长感染性cDNA克隆 | 否 | Liu等[ |
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