The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action.
Adjuvants that can improve mucosal vaccine efficacy are much warranted. In this comparative study between cholera toxin (CT) and immune-stimulating complexes (ISCOM) we found that, contrary to CT, ovalbumin (OVA)-ISCOM were poor inducers of mucosal anti-OVA IgA responses, but induced similar or better systemic immunity following oral immunizations. The addition of CT to the oral OVA-ISCOM protocol did not stimulate local anti-OVA IgA immunity, nor did it change the quality or magnitude of the systemic responses. Both vectors recruited strong innate immunity, but only OVA-ISCOM could directly induce IL-12, demonstrable at the protein and mRNA levels. CT had no inhibitory effects on lipopolysaccharide/IFN-gamma-induced IL-12 mRNA expression or IL-12 production. Furthermore, adjuvanticity of CT was unaffected in IL-12-deficient mice, while OVA-ISCOM showed partly impaired adjuvant effects by the lack of IL-12. CT abrogated the induction of oral tolerance stimulated by antigen feeding in these mice. In addition, CT did not alter TGF-beta levels, suggesting that the immunomodulating effect of CT was independent of IL-12 as well as TGF-beta production. Taken together, these findings indicate that mucosal adjuvanticity of CT and ISCOM are differently dependent on IL-12, suggesting that separate and distinct antigen-processing pathways are involved.
Grdic
D
D
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Smith
R
R
Donachie
A
A
Kjerrulf
M
M
Hörnquist
E
E
Mowat
A
A
Lycke
N
N
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D002772:Cholera Toxin / Q000008:administration & dosage*; D017931:DNA Primers / Q000235:genetics; D016882:ISCOMs / Q000008:administration & dosage*; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D017931:DNA Primers; D016882:ISCOMs; D007074:Immunoglobulin G; D012333:RNA, Messenger; D018664:Interleukin-12; D010047:Ovalbumin; D002772:Cholera Toxin