Safety evaluation of recombinant cholera toxin B subunit produced by Bacillus brevis as a mucosal adjuvant
- 作者：Goto ; Norihisa ; Maeyama ; Jun-ichi ; Yasuda ; Yoko ; Isaka ; Masanori ; Matano ; Keiko ; Kozuka ; Satoshi ; et. al.
- 关键词：Recombinant cholera toxin B subunit (rCTB) ; Intranasal administration ; Mucosal adjuvant ; Safety
- 刊名：Vaccine
- 出版年：2000
- 期刊代码：89_0264410x
- 类别：imm
- 出版时间：April, 2000
- 卷：18
- 期：20
- 页码：2164-2171
- 文件大小：1.35 M
摘要
Mucosal immune responses are known to play important roles in the establishment of protective immunity to microbial infections through mucosa. We examined the toxic effects of recombinant cholera toxin B subunit (rCTB) secreted by Gram-positive bacterium Bacillus brevis as a mucosal adjuvant. Incubation of guinea-pig peritoneal macrophages with cholera toxin (CT) or aluminium hydroxide gel (Al-gel) released a significantly higher activity of lactate dehydrogenase than did commercial natural CTB (CTB) or rCTB. Intraintestinal or intramuscular administration of CT, CTB or Al-gel caused severe histopathological reactions. CT also caused infiltration of neutrophils and irregular arrangement or partial loss of the respiratory epithelium. In addition, CT and CTB elicited vascular permeability-increasing effects. rCTB elicited no toxic effects to macrophages and no vascular permeability-increasing effects. Moreover, it is noticeable that no distinct local histopathological reactions were observed in the nasal cavity, the small-intestinal loop or the muscle given rCTB. These results suggest that, from a safety standpoint, rCTB is a useful candidate as mucosal vaccine adjuvant.