The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action

Grdic, D., Smith, R., Donachie, A., Kjerrulf, M., Hörnquist, E., Mowat, A. and Lycke, N. (1999) The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action. European Journal of Immunology, 29(6), pp. 1774-1784. (doi: 10.1002/(SICI)1521-4141(199906)29:06<1774::AID-IMMU1774>3.0.CO;2-1) (PMID:10382739)

Abstract

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-γ-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-β levels, suggesting that the immunomodulating effect of CT was independent of IL-12 as well as TGF-β 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mowat, Professor Allan and Donachie, Ms Anne Marie
• Authors: Grdic, D., Smith, R., Donachie, A., Kjerrulf, M., Hörnquist, E., Mowat, A., and Lycke, N.
• College/School: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
• Journal Name: European Journal of Immunology
• Journal Abbr.: Eur. J. Immunol.
• Publisher: Wiley - VCH Verlag
• ISSN: 0014-2980
• ISSN (Online): 1521-4141