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 establish ment of protective immunity to microbial infections through mucosa. We exam ined the toxic effects of recombinant cholera toxin B subunit (rCTB) secret ed by Gram-positive bacterium Bacillus brevis as a mucosal adjuvant. Incuba tion of guinea-pig peritoneal macrophages with cholera toxin (CT) or alumin ium hydroxide gel (Al-gel) released a significantly higher activity of lact ate dehydrogenase than did commercial natural CTB (CTB) or rCTB, Intraintes tinal or intramuscular administration of CT, CTB or Al-gel caused seven his topathological reactions. CT also caused infiltration of neutrophils and ir regular arrangement or partial loss of the respiratory epithelium. Ln addit ion, CT and CTB elicited vascular permeability-increasing effects. rCTB eli cited no toxic effects to macrophages and no vascular permeability-increasi ng effects. Moreover, it is noticeable that no distinct local histopatholog ical reactions were observed in the nasal cavity, the small-intestinal loop or the muscle given rCTB. These results suggest that, from a safety standp oint, rCTB is a useful candidate as mucosal vaccine adjuvant. (C) 2000 Publ ished by Elsevier Science Ltd. All rights reserved.