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（Escherichia coli enterotoxin，mLT）的突变体对流感疫苗、麻疹病毒等多种抗原的体液免疫应答具有粘膜佐剂作用，诱导产生高滴度的抗抗原。然而，对于活水痘疫苗（Oka株），它诱导细胞免疫，这对宿主防御VZV感染很重要。将市售的活Oka疫苗病毒和毒素通过鼻途径同时给予小鼠一次。10或12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，但未检测到中和水痘带状疱疹病毒的抗体。用活疫苗和毒素联合免疫的小鼠脾细胞在体外再刺激后，其胸腺嘧啶核苷摄取和IL-2产生均高于单独免疫的小鼠，但低于鼻腔给药后2个月制备的小鼠脾细胞。然而，在这些细胞中的IL-4的产生，并没有诱导体外再刺激。这些结果表明，细胞免疫是诱导和维持超过1年，虽然它随着年龄的增长而下降。结论：水痘-带状疱疹病毒疫苗和mLT鼻腔给药可有效维持机体对水痘-带状疱疹病毒的长期细胞免疫

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。

Hagiwar Y, Tsuji T, et al.: "Effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin (LT1144A) as an adjuvant for nasal influenza vaccine"Vaccine. 19. 2071-2079 (2001)

Hagiwar Y、Tsuji T 等人：“突变型大肠杆菌不耐热肠毒素 (LT1144A) 作为鼻流感疫苗佐剂的有效性和安全性”疫苗。

Jarnicki AG, Tsuji T, et al.: "Hypersensitivity reactions after respiratory sensitization : Effect of intranasal peptides containing T-cell epitopes"J. Allergy. Clin. Immunol.. 110. 610-616 (2002)

Jarnicki AG、Tsuji T 等人：“呼吸致敏后的超敏反应：含有 T 细胞表位的鼻内肽的影响”J。

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

Honma Y，C，Tsuji T 等：“补充磺胺嘧啶的红霉素增强抗志贺菌活性”FEMS 免疫医学微生物学.. 32. 43-46 (2001)