Fragilysin, the enterotoxin from Bacteroides fragilis, enhances the serum antibody response to antigen co-administered by the intranasal route

Fragilysin, an extracellular zinc metalloprotease produced by enterotoxigen ic strains of the anaerobic bacterium Bacteroides fragilis, disrupts the pa racellular barrier by cleavage of the intercellular proteins between epithe lial cells resulting in fluid secretion. Intranasal immunization of mice wi th fragilysin and co-administered ovalbumin (Ova) resulted in an Ova-specif ic serum IgG response that was over 18 000-fold higher than Ova alone, as w ell as detectable levels of serum IgA. Serum IgG titers were comparable wit h those seen when whole cholera toxin was used as the adjuvant, although th e responses obtained with fragilysin showed more variability between mice, Metalloproteases to which fragilysin is structurally related were ineffecti ve as mucosal adjuvants. Our results and similar studies with enterotoxins that affect the paracellular barrier suggest that alteration of mucosal per meability may Flay an important role in the mechanisms of adjuvanticity. (C ) 2000 Elsevier Science Ltd. All rights reserved.