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志贺样毒素-脂质体偶联物诱导小鼠对产细胞毒素的大肠杆菌O157:H7口腔感染产生保护作用

Induction of protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 in mice by shiga-like toxin-liposome conjugate.

作者信息

Fukuda T, Kimiya T, Takahashi M, Arakawa Y, Ami Y, Suzaki Y, Naito S, Horino A, Nagata N, Satoh S, Gondaira F, Sugiyama J, Nakano Y, Mori M, Nishinohara S, Komuro K, Uchida T

机构信息

Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

Int Arch Allergy Immunol. 1998 Aug;116(4):313-7. doi: 10.1159/000023961.

Abstract

We have previously reported that purified Shiga-like toxins (SLT), SLT-I and SLT-II coupled with liposomes induced a substantial amount of anti-SLT-I and anti-SLT-II IgG antibody production, respectively, in mice. The levels of anti-SLT antibody in the sera of SLT-liposome-immune mice correlated well with the protection against subsequent challenge with SLT. In this study, mice were immunized intraperitoneally with the mixture of SLT-I-liposome and SLT-II-liposome and protection against oral infection with cytotoxin-producing Escherichia coli O157:H7 was evaluated. All of the mice that received immunization with the mixture of SLT-I-liposome and SLT-II-liposome were protected against subsequent intravenous challenge with 10 LD50 of either SLT-I or SLT-II. Eight weeks after primary immunization, mice were inoculated intragastrically with 10(9) CFU of E. coli O157:H7 strain 96-60. All SLT-liposome-immune mice tested survived without any apparent symptom while control mice died within 5 days. In addition, as shown by other antigen-liposome conjugates, SLT-liposome induced undetectable anti-SLT IgE antibody production while they induced substantial amounts of anti-SLT IgG antibodies. These results suggest that SLT-liposome conjugate may serve as a candidate vaccine that induces protection against cytotoxin-producing E. coli infection.

摘要

我们先前曾报道,纯化的志贺样毒素(SLT),即SLT-I和SLT-II与脂质体偶联后,分别在小鼠体内诱导产生了大量的抗SLT-I和抗SLT-II IgG抗体。SLT-脂质体免疫小鼠血清中的抗SLT抗体水平与抵抗随后SLT攻击的保护作用密切相关。在本研究中,用SLT-I-脂质体和SLT-II-脂质体的混合物对小鼠进行腹腔免疫,并评估其对产细胞毒素的大肠杆菌O157:H7口服感染的保护作用。所有接受SLT-I-脂质体和SLT-II-脂质体混合物免疫的小鼠,均能抵抗随后10 LD50的SLT-I或SLT-II静脉攻击。初次免疫8周后,给小鼠胃内接种10(9) CFU的大肠杆菌O157:H7菌株96 - 60。所有测试的SLT-脂质体免疫小鼠均存活且无任何明显症状,而对照小鼠在5天内死亡。此外,正如其他抗原-脂质体偶联物所示,SLT-脂质体诱导产生的抗SLT IgE抗体无法检测到,而它们诱导产生了大量的抗SLT IgG抗体。这些结果表明,SLT-脂质体偶联物可能作为一种候选疫苗,诱导对产细胞毒素的大肠杆菌感染的保护作用。

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