Recombinant cholera toxin B subunit is not an effective mucosal adjuvant for oral immunization of mice against Helicobacter felis.
Cholera toxin is a potent oral mucosal adjuvant for enteric immunization. Several studies suggest that commercial cholera toxin B subunit (cCTB; purified from holotoxin) may be an effective non-toxic alternative for oral immunization. The present study was performed, using an infectious disease model, to determine if the oral mucosal adjuvanticity of CTB is dependent on contaminating holotoxin. Mice were orally immunized with Helicobacter felis sonicate and either cholera holotoxin, cCTB or recombinant cholera toxin B subunit (rCTB). Serum immunoglobulin G (IgG) and intestinal immunoglobulin A (IgA) antibody responses were determined and the mice were challenged with live H. felis to determine the degree of protective immunity induced. All orally immunized mice responded with serum IgG antibody titres regardless of the adjuvant used. However, only mice immunized with either holotoxin or the cCTB responded with an intestinal mucosal IgA response. Consistent with the production of mucosal antibodies, mice immunized with either holotoxin or cCTB as adjuvants were protected from challenge while mice receiving H. felis sonicate and rCTB all became infected. cCTB induced the accumulation of cAMP in mouse thymocytes at a level equal to 0.1% of that induced by holotoxin, whereas rCTB was devoid of any activity. These results indicate that CTB possesses no intrinsic mucosal adjuvant activity when administered orally. Therefore, when used as an oral adjuvant, CTB should also include small, non-toxic doses of cholera toxin.
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106-4943, USA.
T G
TG
Blanchard
N
N
Lycke
S J
SJ
Czinn
J G
JG
Nedrud
D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology*; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D016998:Helicobacter / Q000276:immunology; D016481:Helicobacter Infections / Q000517:prevention & control*; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D002772:Cholera Toxin; D000242:Cyclic AMP