"Currently, most if not all vaccines available on the market today contain mineral oil as part of the adjuvant oil phase. In the poultry industry tissue reactions in avian animals injected with mineral oil emulsion vaccines remain a source of poultry condemnations and are of financial concern to the poultry industry. Although the reaction may be due in part to bacterial contamination of the vaccine during use, the mineral oil alone persists for months (Yamamaka et al., Avian Dis. 37:459-466, 1993), may cause undesirable tissue reactions, and is considered to have carcinogenic potential for consumers. To deal with the later concern, a post-vaccination holding period of at least 42 days between vaccination and slaughter has been required for several years (Stone, Avian Diseases 34: 979-983, 1990; Stone, Avian Diseases 37:399-405, 1993, all herein incorporated by reference). Another concern is that accidental injection of operators with mineral oil emulsion is a potential source of liability claims due to personal injury. For these reasons, there is a need for suitable replacements for mineral oil vaccines to be developed. The replacements must have high potency, low viscosity, long shelf life, and minimal tissue reactivity. Also, they must be compatible with mass production techniques, homogenous in appearance, and cost effective.
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Kuroda Y, Akaogi J, Nacionales DC, Wasdo SC, Szabo NJ, Reeves WH, Satoh M.
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.
Although mineral oils are generally considered non-toxic and have a long history of use in humans, the mineral oil Bayol F (incomplete Freund's adjuvant, IFA) and certain mineral oil components (squalene and n-hexadecane) induce lupus-related anti-nRNP/Sm or -Su autoantibodies in non-autoimmune mice. In the present study, we investigated whether medicinal mineral oils can induce other types of autoantibodies and whether structural features of hydrocarbons influence autoantibody specificity. Three-month old female BALB/c (16-45/group) mice received an i.p. injection of pristane (C19), squalene (C30), IFA, 3 medicinal mineral oils (MO-F, MO-HT, MO-S), or PBS. Sera were tested for autoantibodies and immunoglobulin levels. Hydrocarbons were analyzed by gas chromatography/mass spectrometry. IFA contained mainly of C15-C25 hydrocarbons whereas MO-HT and MO-S contained C20-C40 and MO-F contained C15-C40. Pristane and n-hexadecane were found in IFA (0.17% and 0.10%, w/v respectively) and MOs (0.0026-0.027%). At 3 months, pristane and IFA induced mainly IgG2a, squalene IgG1, and MOs IgG3 and IgM in sera. Anti-cytoplasmic antibodies were common in mice treated with MO-F, as well as those treated with pristane, squalene and IFA. Anti-ssDNA and -chromatin antibodies were higher in MO-F and MO-S than in untreated/PBS, squalene, or IFA treated mice, suggesting that there is variability in the induction of anti-nRNP/Sm vs. -chromatin/DNA antibodies. The preferential induction of anti-chromatin/ssDNA antibodies without anti-nRNP/Sm/Su by MO-S and MO-F is consistent with the idea that different types of autoantibodies are regulated differently. Induction of autoantibodies by mineral oils considered non-toxic also may have pathogenetic implications in human autoimmune diseases.