Phytol-based novel adjuvants in vaccine formulation: 1. assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses

So-Yon Lim,Matt Meyer,Richard A Kjonaas,Swapan K Ghosh

doi:10.1186/1476-8518-4-6

Abstract

BackgroundVaccine efficacy depends significantly on the use of appropriate adjuvant(s) in the formulation. Phytol, a dietary diterpene alcohol, is similar in structure to naturally occurring isoprenoid adjuvants; but little is known of its adjuvanticity. In this report, we describe the relative safety and efficacy of phytol and its hydrogenated derivative PHIS-01 compared to commercial adjuvants.MethodsWe tested adjuvant properties using a formulation consisting of either a hapten, phthalate-conjugated to a protein, keyhole limpet hemocyanin (KLH), or ovalbumin (OVA) emulsified with the test adjuvants in mice without any surfactant. Humoral immunity was assessed in terms of titer, specificity, and isotypic profiles. The effect on cell-mediated immunity was studied by assaying the induction of either OVA- or B-lymphoma-specific cytotoxic T-lymphocyte (CTL) activity.Results and DiscussionThe phytol compounds, particularly PHIS-01, elicit increased titers of all major IgG subclasses, especially IgG2a. Unlike commercial adjuvants, both phytol compounds are capable of inducing specific cytotoxic effector T cell responses specific to both OVA and B-lymphoma tested. Phytols as adjuvants are also distinctive in that they provoke no adverse anti-DNA autoimmune response. Intraperitoneally administered phytol is comparable to complete Freund's adjuvant in toxicity in doses over 40 ug/mouse, but PHIS-01 has no such toxicity.ConclusionThese results and our ongoing studies on antibacterial immunity show that phytol and PHIS-01 are novel and effective adjuvants with little toxicity.

Highlights

Vaccine efficacy depends significantly on the use of appropriate adjuvant(s) in the formulation
We demonstrate here that phytol, and to a greater extent phytol-derived PHIS-01, exhibit excellent adjuvanticity at low nontoxic doses and enhance an anti-hapten humoral response that consists of major IgG subclasses, especially IgG2a
Generation of anti-phthalate antibody response in BALB/c mice Groups of 5 mice were injected with 100 μg of phthalateKLH admixed with an adjuvant as described previously [27,28,29]

Summary

Introduction

Vaccine efficacy depends significantly on the use of appropriate adjuvant(s) in the formulation. Vaccine formulations have included specific and safer recombinant proteins, synthetic peptides, and even vectored DNA [1,2] These vaccines are not as effective as those based on whole organisms, but the efficacy is often enhanced when used in conjunction with non-specific immunoadjuvants [3,4,5]. Adjuvants are often foreign to the body and capable of producing adverse reactions These adverse effects can be a direct consequence of toxic or non-metabolizable components in their formulation or can result from the inclusion of agents that overstimulate the immune or inflammatory systems [8]. There is a need for identification of adjuvants that are both safe and efficacious

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Results

Conclusion