In vitro activation of antigen-presenting cells (APC) by defined composition of Quillaja saponaria Molina triterpenoids.
The capacity of adjuvants to stimulate cytokine production by APC is important for the initiation of the immune response. Novel adjuvant formulations based on the iscom technology have been developed using selected triterpenoid components from Quillaja saponaria Molina. Five of these new Quillaja formulations were used to prepare matrix (an antigen-free particle) and tested for their capacity to stimulate IL-1 secretion by murine peritoneal cells in vitro. The formulation denominated QH 7.0.3 was superior to the other matrix formulations, including the original spikoside matrix. The QH 7.0.3 formulation in iscoms containing influenza virus envelope antigens induced IL-1 secretion more efficiently than the antigen-free matrix, or a mixture of matrix and viral antigens, or the free Quillaja components of similar composition. Compared with adjuvants known as IL-1 inducers, QH 7.0.3 flu-iscoms were as efficient as the most prominent IL-1 inducer, i.e. lipopolysaccharide (LPS) and superior to cholera toxin (CT) and muramyl dipeptide (MDP). These results indicate that the composition per se of triterpenoids included in iscoms or matrix has a prominent influence on the level of APC activation which may result in qualitatively different immune responses in vivo.
Behboudi
S
S
Swedish University of Agricultural Sciences, Department of Veterinary Microbiology, Uppsala.
Morein
B
B
Villacres-Eriksson
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology*; D000956:Antigens, Viral / Q000494:pharmacology; D004339:Drug Compounding; D005260:Female; D016882:ISCOMs / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000276:immunology / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D012995:Solubility; D014315:Triterpenes / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D016882:ISCOMs; D007375:Interleukin-1; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; D011112:Polymyxin B