Quillaja saponin formulations that stimulate proinflammatory cytokines elicit a potent acquired cell-mediated immunity

We examined the ability of various Quillaja saponins in iscom-matrix formul ations to induce proinflammatory cytokines, such as interleukin (IL)-1 alph a and IL-6, and to stimulate acquired immune responses to influenza virus e nvelope proteins. The A-fraction of Quillaja saponins (QH-A) was shown to s timulate antigen-presenting cells (APC) to produce proinflammatory cytokine s, and elicited a high primary antigen-specific antibody response and poten t cell-mediated responses, as measured by T-cell proliferation, production of cytokines and cytotoxic T-lymphocyte (CTL) activity. The C-fraction of Q uillaja saponins (QH-C) was shown to have a low capacity to stimulate proin flammatory cytokines and elicited low primary antibody and T-cell responses . However, the QH-C iscom-matrix mediated a potent booster effect, resultin g in a high secondary antibody response. The ability of APC to discriminate and to respond to QH-A formulations more efficiently than to QH-C with rel ease of proinflammatory cytokines, which precedes a potent acquired immune response, identifies an important mechanism through which some adjuvants ma y exert their immunoenhancing activities.