Safety evaluation of recombinant cholera toxin B subunit produced by Bacillus brevis as a mucosal adjuvant.
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.
Goto
N
N
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen, Musashimurayama, Tokyo, Japan. ngoto@nih.go.jp
Maeyama
J
J
Yasuda
Y
Y
Isaka
M
M
Matano
K
K
Kozuka
S
S
Taniguchi
T
T
Miura
Y
Y
Ohkuma
K
K
Tochikubo
K
K
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
D000276:Adjuvants, Immunologic; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D000536:Aluminum Hydroxide; D002772:Cholera Toxin; D007770:L-Lactate Dehydrogenase