Immunostimulatory activity of LT-IIa, a type II heat-labile enterotoxin of Escherichia coli.
Certain bacterial molecules potentiate immune responses to parenterally administered antigens. One such molecule that has been intensely investigated is cholera toxin, a type I heat-labile enterotoxin produced by the Gram-negative bacterium Vibrio cholerae. Immunization with a mixture of a foreign antigen and cholera toxin enhances the immune response to the antigen. Similar adjuvant activity is associated with LT-I, a closely related type I heat-labile enterotoxin produced by Escherichia coli. The adjuvant activities of LT-IIa, a member of the type II heat-labile enterotoxins produced by E. coli, have not been described. LT-IIa and CT differ significantly in amino acid sequence of the B polypeptides and in receptor binding affinity. In this study, rats were subcutaneously immunized with fimbrillin, a protein isolated from the bacterium Porphyromonas gingivalis, and with fimbrillin in combination with LT-IIa, the prototypical type II enterotoxin. Previous studies documented that fimbrillin administered alone is a poor immunogen. Animals immunized with the mixture of fimbrillin and LT-IIa produced high titers of specific IgG antibody directed against fimbrillin. Anti-fimbrillin antibody titers in sera from animals receiving the combination of LT-IIa + fimbrillin were comparable to those obtained from sera of animals immunized with cholera toxin + fimbrillin. The results of these experiments demonstrate that LT-IIa exhibits an adjuvant activity that is equal to that of cholera toxin. Recombinant methods have been established for producing large amounts of LT-IIa, an advantage that will likely provide an economic impetus to consider incorporating the enterotoxin as an immunostimulatory agent in future vaccines.
Department of Microbiology, School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, 14214, USA. tconnell@ubmedd.buffalo.edu
T D
TD
Connell
D
D
Metzger
C
C
Sfintescu
R T
RT
Evans
D000276:Adjuvants, Immunologic; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C063055:fimbrillin; D036781:Fimbriae Proteins; C027538:heat-labile enterotoxin, E coli