IMMUNOMODULATION BYQUILLAJA SAPONARIAADJUVANT FORMULATIONS: IN VIVO STIMULATION OF INTERLEUKIN 12 AND ITS EFFECTS ON THE ANTIBODY RESPONSE

Abstract

The capacity of adjuvants to activate Ag-presenting cells during the induction of the primary immune response is of critical importance for the development of protective immunity to a number of pathogens. In this context, interleukin 12 (IL-12) has a key role by controlling the differentiation of T helper cells and favouring the expansion of Th1cells. The capacity of iscoms with influenza virus Ag (flu-iscoms) and iscom matrix with EBV gp340 Ag to induce IL-12 was analysed in mice. The flu-iscom drives the immune response towards a Th1type subsequent to IL-12 induction as measured in the serum of H2b, H2dand H2kmice. The iscom presenting the Ag and adjuvant in the same particle was considerably more efficient than the formulation of matrix and Ag in separate particles. Inhibition experiments with mAb neutralizing IL-12, interferon gamma (IFN-γ) or IL-4, the latter two cytokines representing the Th1and Th2type of responses, showed that iscoms induce a broader immune response than that involving IL-12. This was shown by the additional effect that IL-4 neutralization had on the immune response to iscoms. Anti-IL 12 reduced the specific total Ab as well as IgG1, IgG2a and IgG2b while anti-IL 4 influenced the response to iscom by decreasing IgG2a and increasing IgG1. Further, the neutralization experiments indicate that IL-12 has a broader effect than IFN-γ on the Ab response by influencing the production of IgG1, IgG2a and IgG2b.