Quillaja Saponin Formulations that Stimulate Proinflammatory Cytokines Elicit a Potent Acquired Cell‐Mediated Immunity

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Abstract
We examined the ability of various Quillaja saponins in iscom‐matrix formulations to induce proinflammatory cytokines, such as interleukin (IL)‐1α and IL‐6, and to stimulate acquired immune responses to influenza virus envelope proteins. The A‐fraction of Quillaja saponins (QH‐A) was shown to stimulate antigen‐presenting cells (APC) to produce proinflammatory cytokines, and elicited a high primary antigen‐specific antibody response and potent cell‐mediated responses, as measured by T‐cell proliferation, production of cytokines and cytotoxic T‐lymphocyte (CTL) activity. The C‐fraction of Quillaja saponins (QH‐C) was shown to have a low capacity to stimulate proinflammatory cytokines and elicited low primary antibody and T‐cell responses. However, the QH‐C iscom‐matrix mediated a potent booster effect, resulting 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 release of proinflammatory cytokines, which precedes a potent acquired immune response, identifies an important mechanism through which some adjuvants may exert their immunoenhancing activities.