Adjuvant action of cholera toxin and pertussis toxin in the induction of IgA antibody response to orally administered antigen.
The ability of cholera toxin B-subunit to bind to intestinal epithelium and in particular the dome epithelium of the Peyer's patch can account for its potency as an immunogen. However, pure B-subunit is a less effective immunogen than whole cholera toxin. The immunogenicity of B-subunit may be restored by the addition of either traces of whole toxin or by pertussis toxin. Cholera toxin and pertussis toxin were both able to stimulate a response when fed in conjunction with keyhole limpet haemocyanin, whereas recombinant B- subunit of heat-labile toxin from Escherichia coli had no effect, demonstrating that the adjuvant action is a property of the enzymically active A-subunits. The adjuvant activity of both pertussis toxin and cholera toxin may be due to their ability to cause an increase in the activity of adenylate cyclase via their action on GTP-binding regulatory proteins. However, feeding of forskolin, a direct activator of adenylate cyclase, had no effect on the mucosal immune response, indicating a role for cholera and pertussis toxin which is independent of enhancement of adenylate cyclase activity in the regulation of the immune response. Antibody to pertussis toxin was not detected, which was attributed to inadequate absorption of pertussis toxin.
University of Bristol, Department of Veterinary Medicine, Langford, UK.
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Wilson
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Robinson
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Irons
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Stokes
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism; D029968:Escherichia coli Proteins; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008808:Mice, Inbred CBA / Q000276:immunology; D037342:Pertussis Toxin; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015290:Second Messenger Systems / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000276:immunology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D006433:Hemocyanins; C027538:heat-labile enterotoxin, E coli; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C032808:keyhole-limpet hemocyanin