Phytol derivatives as novel immunoadjuvants (87.33)

Abstract

Abstract Adjuvants are widely used to influence the course of immune response. Improved adjuvants tailored to immunogens are much sought after. In order to achieve this, we are developing new adjuvants based on chemically modified phytol (J Immune Based Ther. Vaccines 2006, 5:4). We developed hydrogenated/nitrated or glycosylated derivatives of phytol (US patent pending). These compounds exhibit excellent adjuvanticity, and in some respects seem superior to Alum or Freunds’ adjuvants. In this study, we show using cytokine microarray how they influence host microenvironment in the peritoneal lavages of BALB/c mice after injection of phytol adjuvants alone or in combination with different antigens. Our results indicate that 1) within 2 hr after injection there was increase in levels of chemotactic factors MCP-1, KC, MIP-1, LIX and IL-6. 2) The levels of these cytokines were more pronounced with PHIS-01 compared to PHIS-02 and PHIS-03. At 24 hours after injection, the inflammatory cascade was amplified stimulating the production of other cytokines that could involve cells of acquired immunity such as B-lymphocyte chemo-attractant (BLC), T-cell activation-3 (TCA), IL-12 , TIMP-1; in addition, they induced innate immunity-related chemotactic factors. Unlike alum, there was no induction of IL-1β and IL-4 suggesting a different mode of action. We also noted that the cytokine profiles significantly changed when protein antigens were incorporated with the phytol-derived adjuvants.