一种经基因解毒的不耐热大肠杆菌肠毒素衍生物可诱导针对A亚基的中和抗体。
A genetically detoxified derivative of heat-labile Escherichia coli enterotoxin induces neutralizing antibodies against the A subunit.
作者信息
Pizza M, Fontana M R, Giuliani M M, Domenighini M, Magagnoli C, Giannelli V, Nucci D, Hol W, Manetti R, Rappuoli R
机构信息
Immunobiological Research Institute Siena (IRIS), Italy.
出版信息
J Exp Med. 1994 Dec 1;180(6):2147-53. doi: 10.1084/jem.180.6.2147.
Abstract
Escherichia coli enterotoxin (LT) and the homologous cholera toxin (CT) are A-B toxins that cause travelers' diarrhea and cholera, respectively. So far, experimental live and killed vaccines against these diseases have been developed using only the nontoxic B portion of these toxins. The enzymatically active A subunit has not been used because it is responsible for the toxicity and it is reported to induce a negligible titer of toxin neutralizing antibodies. We used site-directed mutagenesis to inactivate the ADP-ribosyltransferase activity of the A subunit and obtained nontoxic derivatives of LT that elicited a good titer of neutralizing antibodies recognizing the A subunit. These LT mutants and equivalent mutants of CT may be used to improve live and killed vaccines against cholera and enterotoxinogenic E. coli.
摘要
大肠杆菌肠毒素（LT）和同源霍乱毒素（CT）是A - B毒素，分别导致旅行者腹泻和霍乱。到目前为止，针对这些疾病的实验性活疫苗和灭活疫苗仅使用了这些毒素的无毒B部分来开发。具有酶活性的A亚基未被使用，因为它具有毒性，并且据报道它诱导产生的毒素中和抗体滴度可忽略不计。我们使用定点诱变使A亚基的ADP - 核糖基转移酶活性失活，并获得了LT的无毒衍生物，其能引发高滴度的识别A亚基的中和抗体。这些LT突变体和CT的等效突变体可用于改进针对霍乱和产肠毒素大肠杆菌的活疫苗和灭活疫苗。
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