Analysis of adjuvant action Escherichia coli enterotoxin

大肠杆菌肠毒素的佐剂作用分析

• 批准号: 13670285
• 负责人: TSUJI Takao
• 金额: $ 1.98万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670285/
• 关键词: ETEC; LT; adjuvant action; Oka vaccine; cellular immunity; VZV; αβT cells; γδT cells; 粘膜アジバント; 易熱下痢毒素(LT); B1細胞

A mutant of Escherichia coli enterotoxin (mLT) has mucosal adjuvant action to humoral immuno-response for various antigens like influenza vaccine or measles virus and induced high titers of anti-antigen. However, for a live varicella vaccine (the Oka strain), it induced cellular immunity, which is important for host defense for VZV infection. A commercially available live Oka vaccine virus and toxin were administered once simultaneously via the nasal route, in mice. Ten or 12 months later, a delayed-type hypersensitivity to the vaccine virus was detected by footpad test, but an antibody neutralizing the varicella-zoster virus was not. When spleen cells from mice immunized with the vaccine and toxin were re-stimulated by live vaccine in vitro, their thymidine uptake and IL-2 production were higher than those from mice immunized with the vaccine alone, but lower than those of spleen cells prepared from mice 2 months after nasal administration. Production of IL-4 in these cells, however, was not induced by re-stimulation in vitro. These results suggest that cellular immunity is induced and maintained over 1 year, though it declines with age. The nasal administration of the vaccine and mLT might be effective for maintaining cellular immunity to the varicella-zoster virus long term

大肠杆菌肠毒素（mLT）的突变体对流感疫苗或麻疹病毒等各种抗原的体液免疫应答具有粘膜佐剂作用，并诱导高滴度的抗抗原。然而，对于水痘活疫苗（Oka 株）来说，它可以诱导细胞免疫，这对于宿主防御水痘带状疱疹病毒感染非常重要。通过鼻腔途径对小鼠同时施用市售的活奥卡疫苗病毒和毒素。十或十二个月后，通过足垫试验检测到对疫苗病毒的迟发型超敏反应，但没有检测到中和水痘带状疱疹病毒的抗体。当用疫苗和毒素免疫的小鼠的脾细胞在体外用活疫苗重新刺激时，其胸苷摄取和IL-2的产生高于单独用疫苗免疫的小鼠，但低于用活疫苗制备的脾细胞。鼻腔给药后 2 个月的小鼠。然而，这些细胞中IL-4的产生并不是通过体外再刺激来诱导的。这些结果表明细胞免疫被诱导并维持超过一年，尽管它随着年龄的增长而下降。鼻腔注射疫苗和 MLT 可能有助于长期维持对水痘带状疱疹病毒的细胞免疫

项目成果

Jarniki, A.G., Tsuji T., Thomas, W.R.: "Inhibition of mucosal and systemic Th2 immune response by intran asal peptides containing a dominat T cell epitope of the allergen Der p1"Internal Immunology. 13(10). 1223-1231 (2001)

Jarniki, A.G.、Tsuji T.、Thomas, W.R.：“含有过敏原 Der p1 的主要 T 细胞表位的鼻内肽抑制粘膜和全身 Th2 免疫反应”内部免疫学。

Mahamut N, Inoue K, Tsuji T, Arimitu H, Oguma K, et al: "Mocosal immunization with Clostridium botulinum type C 16 S toxoid and its non-toxic component"J. Med. Microbiol.. 51. 813-820 (2002)

Mahamut N、Inoue K、Tsuji T、Arimitu H、Oguma K 等人：“用肉毒梭菌 C 16 S 型类毒素及其无毒成分进行粘膜免疫”J。

Kamiya N, Asano Y, Yoshino J, Sasaki K, Honma Y, Kawase H, Yokochi T, Shiraki K, Tsuji T: "Long-term persistence of cellular immunity to Oka vaccine virus induced by pernasal co-administration with Escherichia coli enterotoxin in mice"Vaccine. 30 ; 19(23-

Kamiya N、Asano Y、Yoshino J、Sasaki K、Honma Y、Kawase H、Yokochi T、Shiraki K、Tsuji T：“经鼻与大肠杆菌肠毒素共同给药诱导的对 Oka 疫苗病毒的细胞免疫的长期持续性

Mahamut N, Tsuji T. et al.: "Mocosal immunization with Clostridium botulinum type C 16 S toxoid and its non-toxic component"J. Med. Microbiol.. 51. 813-820 (2002)

Mahamut N, Tsuji T. 等人：“用肉毒梭菌 C 16 S 类毒素及其无毒成分进行粘膜免疫”J.

Honma Y, C, Tsuji T et al.: "Enhanced anti-Shigella activity of erythroinycin supplemented with sulfadiazine"FEMS immunol Med Microviol.. 32. 43-46 (2001)

Honma Y, C, Tsuji T 等人：“补充有磺胺嘧啶的红霉素增强抗志贺菌活性”FEMSimmunolMedMicroviol.. 32. 43-46 (2001)