Abstract

BackgroundVaccines have profoundly impacted global health although concerns persist about their potential role in autoimmune or other adverse reactions. To address these concerns, vaccine components like immunogens and adjuvants require critical evaluation not only in healthy subjects but also in those genetically averse to vaccine constituents. Evaluation in autoimmune-prone animal models of adjuvants is therefore important in vaccine development. The objective here was to assess the effectiveness of experimental adjuvants: two phytol-derived immunostimulants PHIS-01 (phytanol) and PHIS-03 (phytanyl mannose), and a new commercial adjuvant from porcine small intestinal submucosa (SIS-H), relative to a standard adjuvant alum. Phytol derivatives are hydrophobic, oil-in water diterpenoids, while alum is hydrophilic, and SIS is essentially a biodegradable and collagenous protein cocktail derived from extracellular matrices.ResultsWe studied phthalate -specific and cross-reactive anti-DNA antibody responses, and parameters associated with the onset of autoimmune disorders. We determined antibody isotype and cytokine/chemokine milieu induced by the above experimental adjuvants relative to alum. Our results indicated that the phytol-derived adjuvant PHIS-01 exceeded alum in enhancing anti-phthalate antibody without much cross reactivity with ds-DNA. Relatively, SIS and PHIS-03 proved less robust, but they were also less inflammatory. Interestingly, these adjuvants facilitated isotype switching of anti-hapten, but not of anti-DNA response. The current study reaffirms our earlier reports on adjuvanticity of phytol compounds and SIS-H in non autoimmune-prone BALB/c and C57BL/6 mice. These adjuvants are as effective as alum also in autoimmune-prone NZB/WF1 mice, and they have little deleterious effects.ConclusionAlthough all adjuvants tested impacted cytokine/chemokine milieu in favor of Th1/Th2 balance, the phytol compounds fared better in reducing the onset of autoimmune syndromes. However, SIS is least inflammatory among the adjuvants evaluated.

Highlights

  • Vaccines have profoundly impacted global health concerns persist about their potential role in autoimmune or other adverse reactions

  • Effects of adjuvants on antibody response to phthalate in NZB/WF1 mice Anti-phthalate antibody responses were induced in NZB/ W F1 mice (8 weeks old) by repeated vaccination and sera assayed for evaluation of adjuvants

  • The phytol derivative Phytol-based immune-stimulant (PHIS)-01 enhanced antibody titer 10fold over what was registered with Porcine small intestinal submucosa (SIS)-H, PHIS-03, and alum

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Summary

Introduction

Vaccines have profoundly impacted global health concerns persist about their potential role in autoimmune or other adverse reactions. We observed that modified phytol compounds such as PHIS-01 (Phytanol) and PHIS-03 (Phytanyl mannose) are safe and highly effective adjuvants in immunocompetent inbred strains of mice, BALB/c and C57BL/6 [3,4,7,8]. They enhance immunogenicity of many soluble protein antigens and of heat-killed pathogens [3,4,7,8]. This necessitates an evaluation of putative adjuvants alone and in combination with vaccine materials in both normal and compromised subjects

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