title: Safety evaluation of recombinant cholera toxin B subunit produced by Bacillus brevis as a mucosal adjuvant.
abstract: 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.
authors.affiliation: Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen, Musashimurayama, Tokyo, Japan. ngoto@nih.go.jp
authors.forename: N
authors.initials: N
authors.lastname: Goto
authors.forename: J
authors.initials: J
authors.lastname: Maeyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuda
authors.forename: M
authors.initials: M
authors.lastname: Isaka
authors.forename: K
authors.initials: K
authors.lastname: Matano
authors.forename: S
authors.initials: S
authors.lastname: Kozuka
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Ohkuma
authors.forename: K
authors.initials: K
authors.lastname: Tochikubo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity*; D000281:Administration, Intranasal; D000536:Aluminum Hydroxide; D000818:Animals; D001407:Bacillus / Q000378:metabolism*; D019559:Capillary Leak Syndrome / Q000209:etiology; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D007249:Inflammation / Q000209:etiology; D007267:Injections; D007273:Injections, Intramuscular; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology; D009296:Nasal Cavity / Q000473:pathology; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000633:toxicity*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D012449:Safety
chemical_list: D000276:Adjuvants, Immunologic; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D000536:Aluminum Hydroxide; D002772:Cholera Toxin; D007770:L-Lactate Dehydrogenase