Subunit vaccine against the seven serotypes of botulism
Subunit vaccine against the seven serotypes of botulism
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DOI：
10.1128/iai.01025-07
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发表时间：
2008-03-01
影响因子：
3.1
通讯作者：
Barbieri, Joseph T.
中科院分区：
文献类型：
--
作者：
Baldwin, Michael R.;Tepp, William H.;Barbieri, Joseph T.
肉毒神经毒素（Botanicneurotoxins，BoNTs）是对人类毒性最大的蛋白质，被归类为A类毒素。存在由缺乏交叉血清型毒素中和定义的七种BoNT血清型。因此，有效的疫苗必须中和每种BoNT血清型。BoNT组织为双链A-B毒素，其中N-末端结构域（轻链）是靶向可溶性NSF附着受体蛋白的锌金属蛋白酶，其通过二硫键与C-末端结构域（重链[HC]）连接。HC包含易位结构域和C末端受体结合结构域（HCR）。将七种血清型BoNT的HCR（hepta-HCR）工程化以用于在大肠杆菌中表达，并且从大肠杆菌中纯化每种HCR。大肠杆菌裂解物。用E.大肠杆菌衍生的七血清型HCR疫苗引发了对七种BoNT HCR中的每一种的抗体应答，并中和了七种BoNT血清型中的每一种的10，000 50%致死剂量的攻击。固相分析显示，抗七血清型HCR血清抑制HCR血清型A和B与神经节苷脂GT 1 B b的结合，这是BoNT中毒神经元的第一步。这是第一个E。大肠杆菌衍生的疫苗，有效地中和每一个七BoNT血清型。
Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans and are classified as category A toxins. There are seven serotypes of BoNTs defined by the lack of cross-serotype toxin neutralization. Thus, an effective vaccine must neutralize each BoNT serotype. BoNTs are organized as dichain A-B toxins, where the N-terminal domain (light chain) is a zinc metalloprotease targeting soluble NSF attachment receptor proteins that is linked to the C-terminal domain (heavy chain [HC]) by a disulfide bond. The HC comprises a translocation domain and a C-terminal receptor binding domain (HCR). HCRs of the seven serotypes of BoNTs (hepta-HCR) were engineered for expression in Escherichia coli, and each HCR was purified from E. coli lysates. Immunization of mice with the E. coli-derived hepta-serotype HCR vaccine elicited an antibody response to each of the seven BoNT HCRs and neutralized challenge by 10,000 50% lethal doses of each of the seven BoNT serotypes. A solid-phase assay showed that the anti-hepta-serotype HCR sera inhibited the binding of HCR serotypes A and B to the ganglioside GT1b, the first step in BoNT intoxication of neurons. This is the first E. coli-derived vaccine that effectively neutralizes each of the seven BoNT serotypes.