Bacteriophage-mediated nucleic acid immunisation

Bacteriophage-mediated nucleic acid immunisation
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DOI:
10.1016/s0928-8244(03)00344-4
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发表时间:
2004-01-15
影响因子:
--
通讯作者:
March, JB
March, JB
中科院分区:
其他
文献类型:
--
作者:
Clark, JR;March, JB

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含有在巨细胞病毒启动子(P-CMV)控制下的报告基因的完整噬菌体λ颗粒已被用作核酸免疫的递送载体。小鼠肌肉注射含有B型肝炎表面抗原(HBsAg)基因的IgGda-gt 11后,检测到超过150 mIU ml(-1)的抗HBsAg应答。当分离的腹腔巨噬细胞与含有绿色荧光蛋白(GFP)基因的完整λ颗粒在P-CMV的控制下孵育时,8小时后在巨噬细胞表面检测到GFP抗原。结果表明,噬菌体“疫苗”可能直接靶向抗原呈递细胞,与裸DNA递送相比,导致增强的免疫应答。噬菌体DNA疫苗具有几个优点:它们不含抗生素抗性基因,它们提供大的克隆能力(类似于15 kb),DNA被保护免受环境降解,它们提供口服递送的可能性,并且大规模生产便宜,容易且非常快速。(C)2003年,欧洲微生物学会联合会。Elsevier B. V.出版,保留所有权利。
Whole bacteriophage lambda particles, containing reporter genes under the control of the cytomegalovirus promoter (P-CMV), have been used as delivery vehicles for nucleic acid immunisation. Following intramuscular injection of mice with lambda-gt11 containing the gene for hepatitis B surface antigen (HBsAg), anti-HBsAg responses in excess of 150 mIU ml(-1) were detected. When isolated peritoneal macrophages were incubated with whole lambda particles containing the gene for green fluorescent protein (GFP) under the control of P-CMV, GFP antigen was detected on the macrophage surface 8 h later. Results suggested that direct targeting of antigen-presenting cells by bacteriophage 'vaccines' may occur, leading to enhanced immune responses compared to naked DNA delivery. Bacteriophage DNA vaccines offer several advantages: they do not contain antibiotic resistance genes, they offer a large cloning capacity (similar to15 kb), the DNA is protected from environmental degradation, they offer the potential for oral delivery, and large-scale production is cheap, easy and extremely rapid. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.