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 activation of antigen-presenting cells (APC), a prerequisite for the development of immune responses. Interleukin 6 (IL-6) has been identified as a key factor in the generation of cytolytic T lymphocytes, which constitute an important effector mechanism elicited by immuno-stimulatory complex (iscom)-borne antigens. To identify factors relevant to the unique property of iscoms to mediate CTL responses, we analysed the capacity of different defined Quillaja triterpenoid components in various formulations to stimulate production of IL-6 by APC in vitro and in vivo. The iscom formed with Quillaja adjuvant and incorporated influenza virus envelope proteins elicited the highest secretion of IL-6. The production of IL-6 was also stimulated by the antigen free matrix of the iscom and even by the Quillaja triterpenoids as free components albeit 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 vs 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.
Behboudi
S
S
Swedish University of Agricultural Sciences, Department of Veterinary Microbiology, Uppsala, Sweden.
Morein
B
B
Villacres-Eriksson
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D006388:Hemagglutinins / Q000008:administration & dosage / Q000302:isolation & purification; D016882:ISCOMs / Q000008:administration & dosage / Q000494:pharmacology*; D009980:Influenza A virus / Q000737:chemistry; D015850:Interleukin-6 / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000008:administration & dosage / Q000302:isolation & purification; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000302:isolation & purification
D000276:Adjuvants, Immunologic; D006388:Hemagglutinins; D016882:ISCOMs; D015850:Interleukin-6; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; D014759:Viral Envelope Proteins; D009439:Neuraminidase; D011112:Polymyxin B