Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT):: potatoes expressing a synthetic LT-B gene
Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT):: potatoes expressing a synthetic LT-B gene
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DOI：
10.1016/s0264-410x(98)80020-0
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发表时间：
1998-08-01
期刊：
影响因子：
5.5
通讯作者：
Arntzen, CJ
中科院分区：
文献类型：
--
作者：
Mason, HS;Haq, TA;Arntzen, CJ
作者设计并构建了一种植物优化的合成基因，编码大肠杆菌热不稳定肠毒素B亚基（LT-B），用于转基因植物作为抗肠毒素E的可食用疫苗。在马铃薯植物中，合成的LT-B基因在组成启动子的控制下表达，与细菌的LT-B基因相比，在叶片和块茎中增加了LT-B的积累。植物衍生的LT-B组装成天然五聚体结构，其结合神经节苷脂的能力证明了这一点。作者通过给小鼠喂食生块茎，并将其抗LT-B血清IgG和粪便IgA与细菌LT-B灌胃小鼠产生的抗体进行比较，证明了其免疫原性。小鼠每3次给予含20或50 μ g LT-B的块茎组织5g，或每周灌胃5 μ g重组大肠杆菌LT-B。第三次鼻后1周，马铃薯LT-B免疫小鼠血清和黏膜抗LT-B水平高于细菌LT-B灌胃小鼠。小鼠口服25 μ g LT，并通过比较肠道/胴体质量比来评估保护作用。尽管没有小鼠完全受到保护，但高剂量马铃薯疫苗与细菌疫苗相比味道更好。这些发现表明，一种针对大肠杆菌LT-B的可食用疫苗是可行的。1998爱思唯尔科学有限公司版权所有。
The authors have designed and constructed a plant-optimized synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E, coli Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to the bacterial LT-B gene. The plant-derived LT-B assembled into native pentameric structures as evidenced by its ability to bind ganglioside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the anti-LT-B serum IgG and faecal IgA to that produced in mice gavaged with bacterial LT-B. Mice were fed three weekly doses of 5g tuber tissue containing either 20 or 50 mu g LT-B, or gavaged weekly with 5 mu g of LT-B from recombinant E, coli One week after the third nose, mice immunized with potato LT-B had higher levels of serum and mucosal anti-LT-B than those gavaged with bacterial LT-B. Mice were challenged by oral administration of 25 mu g LT and protection assessed by comparing the gut/carcass mass ratios, Although none of the mice were completely protected, the higher dose potato vaccine compared flavourably with the bacterial vaccine. These findings show that an edible vaccine against E, coli LT-B is feasible. (C) 1998 Elsevier Science Ltd. All rights reserved.