IN-VIVO AND IN-VITRO INDUCTION OF IL-6 BY QUILLAJA-SAPONARIA MOLINA TRITERPENOID FORMULATIONS

Quillaja saponaria Molina and some of the defined Quillaja components are potent adjuvants, An important function of adjuvants is the activa tion of antigen-presenting cells (APC), a prerequisite for the develop ment of immune responses, Interleukin 6 (IL-6) has been identified as a key factor in the generation of cytolytic T lymphocytes, which const itute an important effector mechanism elicited by immune-stimulatory c omplex (iscom)-borne antigens, To identify factors relevant to the uni que property of iscoms to mediate CTL responses, we analysed the capac ity of different defined Quillaja triterpenoid components in various f ormulations to stimulate production of IL-6 by APC in vitro and in viv o. The iscom formed with Quillaja adjuvant and incorporated influenza virus envelope proteins elicited the highest secretion of IL-6, The pr oduction of IL-6 was also stimulated by the antigen free matrix of the iscom and even by the Quillaja triterpenoids as free components albei t to a significantly lesser extent. Among the various combinations of QH-A and QH-C tested and also the original semipurified spikoside, the QH 7.0.3 matrix was the most efficient formulation for activation of IL-6 production by APC, In general, an increasing proportion of QH-A v s QH-C increases the capacity to activate APC, The results demonstrate that the incorporated antigen and the adjuvant component in the same particle have the synergistic effects on immunogenicity. (C) 1997 Acad emic Press Limited.