IMMUNOSTIMULATORY ACTIVITY OF LT-IIA, A TYPE-II HEAT-LABILE ENTEROTOXIN OF ESCHERICHIA-COLI

Certain bacterial molecules potentiate immune responses to parenterall y administered antigens. One such molecule that has been intensely inv estigated is cholera toxin, a type I heat-labile enterotoxin produced by the Gram-negative bacterium Vibrio cholerae. Immunization with a mi xture of a foreign antigen and cholera toxin enhances the immune respo nse to the antigen. Similar adjuvant activity is associated with LT-I, a closely related type I heat-labile enterotoxin produced by Escheric hia coli. The adjuvant activities of LT-IIa, a member of the type II h eat-labile enterotoxins produced by E. coli, have not been described. LT-IIa and CT differ significantly in amino acid sequence of the B pol ypeptides and in receptor binding affinity. In this study, rats were s ubcutaneously immunized with fimbrillin, a protein isolated from the b acterium Porphyromonas gingivalis, and with fimbrillin in combination with LT-IIa, the prototypical type II enterotoxin. Previous studies do cumented that fimbrillin administered alone is a poor immunogen. Anima ls immunized with the mixture of fimbrillin and LT-IIa produced high t iters of specific IgG antibody directed against fimbrillin. Anti-fimbr illin antibody titers in sera from animals receiving the combination o f LT-IIa + fimbrillin were comparable to those obtained from sera of a nimals immunized with cholera toxin + fimbrillin. The results of these experiments demonstrate that LT-IIa exhibits an adjuvant activity tha t is equal to that of cholera toxin. Recombinant methods have been est ablished for producing large amounts of LT-IIa, an advantage that will likely provide an economic impetus to consider incorporating the ente rotoxin as an immunostimulatory agent in future vaccines. (C) 1998 Els evier Science B.V. All rights reserved.