Novel phytol-based adjuvants in vaccine formulations: Evaluation of safety and efficacy in induction and persistence of specific immune responses (41.64)

Abstract

Abstract Adjuvants function as "immunologists' dirty tricks" for enhancement of immune response. However, no two adjuvants work in a similar fashion. Adjuvant efficacy depends on how they influence microenvironment, antigen presentation and retention of immunogens. We are developing water-in-oil emulsion-type adjuvants from phytol (J Immune Based Ther Vaccines 2006, 5:4; ibid 2007; 5: 3). Phytol is a diterpene present in chlorophylls, alpha-tocopherols etc. Phytol derivatives we developed are hydrogenated/nitrated and glycosylated products (US patent pending). Our previous study showed that one phytol derivative PHIS-01(hydrogenated) is an excellent non-toxic adjuvant. In this study, we investigated the safety and efficacy of two other phytol compounds, PHIS-02 and PHIS-03 relative to PHIS-01 and other adjuvants. Using phthalate- keyhole limpet hemocyanin (KLH) conjugate as the immunogen emulsified with these adjuvants, we assessed titer, specificity, and isotypic profiles of anti-phthalate antibodies induced. In addition, we studied their effects on cellular immunity such as T cell proliferation and cytokine production. Preliminary results show that (1) phytol adjuvants significantly augment antibody response of isotypes IgG1 and IgG2a, (2) promote effective T cell proliferation, and (3) exhibit low toxicity with no adverse autoimmune anti-DNA response. We also observed that these adjuvants exert apoptotic/necrotic effects on mouse lymphoma cells 2C3 and A20 in a concentration-dependent manner.