Development of effective mucosal vaccine against bacterial afferent infectious diseases

开发针对细菌性传入传染病的有效粘膜疫苗

• 批准号: 15590395
• 负责人: TANIGUCHI Toru
• 金额: $ 1.73万
• 依托单位: NAGOYA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590395/
• 关键词: enterotoxigenic Escherichia coli; Vibrio parahaemolyticus; pili; colonization factor; adhesin; thermostable direct hemolvsin; mucosal vaccine; immune response

For prevention (vaccine) of enterotoxigenic Escherichia coli (ETEC) and Vibrio parahaemolyticus infections, it is important to stimulate the production of mucosal secretory immunoglobulin A (sIgA) for blocking of colonization to intestinal epithelium and neutralizing of toxins. Recombinant cholera toxin B subunit (rCTB) was used as a mucosal adjuvant.1. Purification of vaccine antigenAdhesins (CfaE and CofJ) of pilus colonization factor antigens (CFA/I and CFA/III) of ETEC and less hemolytic mutant toxin of thermostable direct hemolysin (mTDH) of V. parahaemolyticus were purified by using His-tag fusion vector (pQE-30Xa).2. Immune response in experiment animalIntranasal administration of CfaE or CofJ to BALB/c mice with and without rCTB induced CfaE-and CofJ-specific serum IgG and mucosal immune response (sIgA) in the saliva, the nasal cavity, the lung, the vagina, the small intestine and the feces.BALB/c mice immunized intranasally with mTDH irrespective of the presence of rCTB showed TDH-specific serum IgG antibody response and mucosal immune response (sIgA), especially in the lung and the small intestine. Moreover, mice immunized could protect against lethal challenge with wild-type TDH.

为了预防（疫苗）产肠毒素大肠杆菌（ETEC）和副溶血性弧菌感染，刺激粘膜分泌免疫球蛋白A （sIgA）的产生是重要的，它可以阻断肠道上皮定植和中和毒素。重组霍乱毒素B亚基（rCTB）作为粘膜佐剂。疫苗抗原的纯化利用His-tag融合载体（pQE-30Xa）纯化ETEC菌毛定植因子抗原（CFA/I和CFA/III）粘附素（CfaE和CofJ）和副溶血性弧菌热稳定型直接溶血素（mTDH）少溶血突变毒素2。实验动物的免疫反应：经鼻给药CfaE或CofJ可诱导唾液、鼻腔、肺、阴道、小肠和粪便中CfaE和CofJ特异性血清IgG和黏膜免疫反应（sIgA）。不论rCTB是否存在，经鼻内接种mTDH的BALB/c小鼠均表现出tdh特异性血清IgG抗体反应和粘膜免疫反应（sIgA），尤其是在肺和小肠。此外，免疫小鼠对野生型TDH的致命攻击具有保护作用。

项目成果

Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine.

重组霍乱毒素 B 亚基 (rCTB) 作为粘膜佐剂，通过鼻内注射白喉-百日咳-破伤风 (DPT) 联合疫苗，增强小鼠白喉和破伤风抗毒素抗体的诱导。

• 发表时间: 2004
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: M. Isaka;T. Komiya;Motohide Takahashi;Y. Yasuda;T. Taniguchi;Yanqiu Zhao;K. Matano;H. Matsui;J. Maeyama;K. Morokuma;K. Ohkuma;N. Goto;K. Tochikubo
• 通讯作者: K. Tochikubo

Isaka, Masanori: "Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant"Vaccine. 21・11-12. 1165-1173 (2003)

Isaka，Masanori：“与重组霍乱毒素 B 亚基作为佐剂鼻内共同给药后，小鼠体内针对无细胞百日咳疫苗的粘膜和全身抗体反应”疫苗 21·11-12。

Frequent nasal administrations of recombinant cholera toxin B subunit (rCTB)-containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum and mucosal immune responses in the presence of anti-rCTB antibodies

频繁鼻腔注射含有重组霍乱毒素 B 亚基 (rCTB) 的破伤风和白喉类毒素疫苗，在抗 rCTB 抗体存在的情况下可诱导抗原特异性血清和粘膜免疫反应

• 发表时间: 2003
• 期刊: Vaccine 21(21/22)
• 作者: Isaka;Masanori;Yasuda Yoko et al.
• 通讯作者: Yasuda Yoko et al.

Yasuda, Yoko: "Frequent nasal administrations of recombinant cholera toxin B subunit(rCTB)-containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum and mucosal immune responses in the presence of anti-rCTB antibodies"Vaccine. 21・21

安田洋子：“频繁鼻腔注射含有重组霍乱毒素 B 亚基 (rCTB) 的破伤风和白喉类毒素疫苗，在抗 rCTB 抗体存在的情况下诱导抗原特异性血清和粘膜免疫反应”疫苗 21・21。

Effects of Recombinant Cholera Toxin B Subunit (rCTB) on Cellular Immune Responses: Enhancement of Delayed‐Type Hypersensitivity Following Intranasal Co‐Administration of Mycobacterium bovis‐BCG with rCTB

重组霍乱毒素 B 亚基 (rCTB) 对细胞免疫反应的影响：牛分枝杆菌-BCG 与 rCTB 鼻内联合给药后迟发型超敏反应增强

• DOI: 10.1111/j.1348-0421.2004.tb03536.x
• 发表时间: 2004
• 期刊: Microbiology and Immunology
• 影响因子: 2.6
• 作者: J. Maeyama;M. Isaka;Y. Yasuda;K. Matano;K. Morokuma;K. Ohkuma;K. Tochikubo;Saburo Yamamoto;N. Goto
• 通讯作者: N. Goto