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Background  Adjuvants are known to significantly enhance vaccine efficacy. However, commercial adjuvants often have limited use because of toxicity in humans. The objective of this study was to determine the comparative effectiveness of a diterpene alcohol, phytol and its hydrogenated derivative PHIS-01, relative to incomplete Freund's adjuvant (IFA), a commonly used adjuvant in augmenting protective immunity in mice against  E. coli  and  S. aureus , and in terms of inflammatory cytokines.    Methods  Vaccines, consisting of heat-attenuated  E. coli  or  S. aureus  and either of the two phytol-based adjuvants or IFA, were tested in female BALB/c mice. The vaccines were administered intraperitoneally at 10-day intervals. The efficacy of the phytol and PHIS-01, as compared to IFA, was assessed by ELISA in terms of anti-bacterial antibody and inflammatory cytokines. We also examined the ability of the vaccines to induce specific protective immunity by challenging mice with different doses of live bacteria.    Results and discussion  IFA, phytol, and PHIS-01 were equally efficient in evoking anti- E. coli  antibody response and in providing protective immunity against live  E. coli  challenges. In contrast, the antibody response to  S. aureus  was significant when PHIS-01 was used as the adjuvant. However, in terms of the ability to induce protective immunity, phytol was most effective against  S. aureus . Moreover, during challenges with live  E. coli  and  S. aureus  immune mice produced much less IL-6, the mediators of fatal septic shock syndromes.    Conclusion  Our results show that vaccine formulations containing phytol and PHIS-01 as adjuvants confer a robust and protective immunity against both Gram-negative and Gram-positive bacteria without inducing adverse inflammatory cytokine due to IL-6.

journal of immune based therapies and vaccines

Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice