Date of Award
Spring 3-1-2014
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biology
Abstract
The main objective of this study is to evaluate an oil-in-water micro-emulsion of phytanol which we have named PHIS59 with multiple antigens: ovalbumin, a protein and microorganism that include a reference laboratory strain of methicillin susceptible Staphylococcus aureus (MSSA) and methicillin resistant S. aureus (MRSA). PHIS59 was compared with the previously described crude oil-in-water emulsion PHIS-01 and the similarly formulated squalene as an oil-in-water micro-emulsion based on the commercial product MF59 referred to here as NV59. Safety and efficacy of PHIS59 and NV59 was evaluated in a mouse and rabbit vaccine models. Determinations of safety were reported as the range of in vivo mouse LD50s for each compound. Vaccine efficacy was assessed in terms of antibody response titers and isotype profiles in sera of vaccinated animals. Vaccines consisted of ovalbumin or heat killed S. aureus adjuvanted with either PHIS59, NV59 or PHIS-01. Control animals received unadjuvanted controls. Currently, there is no approved MRSA vaccine. PHIS-01 has shown promise in preventing MRSA-associated mortality in a mouse model; this study provides cross species validation. PHIS59 is easier to handle than PHIS-01 because it does not bind the syringe plunger, can be preloaded into syringes and is a stable emulsion which allows consistent dose delivery. PHIS59 has a lower LD50 but is effective at lower doses giving a similar therapeutic index. This iv could be explained by increased bioavailability due to the micro-emulsion formulation. This is an improvement over PHIS-01 in that it is effective at lower doses. Finally, we tested a novel water soluble phytol derivative, sodium phytanyl sulfate and characterized a safe working dose range. Based on the doses determined through this study, sodium phytanyl sulfate (PHIS-SO4) is currently being studied as an adjuvant with an effective mouse dose of less than 1mg. Additionally, because it is soluble in water, it requires no emulsification for formulation in vaccines.
Recommended Citation
Johnson, Dylan M., "Phytol Derived Immunoadjuvants as Oil-in-water Micro-emulsions For Use in Vaccines" (2014). All-Inclusive List of Electronic Theses and Dissertations. 128.
https://scholars.indianastate.edu/etds/128
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