Enepret Incorporated — Department of Health and Human Services STTR Phase I: NIAID

Description

ABSTRACT Vaccine adjuvants help stimulate the body to generate an immune response when co injected with an antigenthe compound for which immunity is desiredAlthough the human body is capable of producing antibodies to most injected antigensadjuvants can help boost the body s ability to mount a successful and acquired immune response to the presented targetAdjuvants have been shown to enhance immunity against targets that usually exhibit poor immune responses such as highly purified and recombinantly produced antigensThis is particularly important for individuals which may have a less robust immune systemsuch as children or the elderlyOne of the well studied adjuvants that is approved for use in humans nearly worldwide is the oil in water emulsionMFThe oil used in this formulation is the hydrocarbon triterpenesqualeneSqualene is a natural oil produced in all eukaryotic organisms as it is the precursor to sterolse gcholesterolMFis a component of Fluadan FDA approved seasonal influenza vaccine for peopleyears oldThe traditional source of squalene has been from shark liver oilwhich is no longer viable nor sustainableIn light of these limitationsand the desire to develop more efficacious adjuvantsfermentable yeast and transgenic plants have been engineered to produce high amounts of squalene and several relatednovel triterpenesThese include botryococcene plus monoand di methylated forms of squalene and botryococceneThe experiments proposed here are designed to accomplish two specific aimsusing a mouse modeldemonstrate that our Synthetic Biology generated squalene performs equivalent to shark derived squalene in adjuvant vaccine formulationsandevaluate ournovel triterpenes in adjuvant formulations for their abilities to induce elevated or altered immune responses compared to squaleneOur studies will quantitatively compare the immunogenicity of a trivalent influenza vaccine plus and minus the different triterpene adjuvant formulations by measuring antibodyIgGIgG a and IgEand hemagglutination inhibitionHItitersThe possibility that our antigen triterpene adjuvant formulations might induce undesirable effects will be assessed by measuring inflammatory cytokine levels in sera samples of the inoculated animalsOnce the feasibility of using these compounds in an adjuvant system is demonstrated in this Phase I studythe foundation for several follow on Phase II studies will be establishedonedemonstrating the biological equivalency of our Synthetic Biology produced squalene would endorse efforts to use process engineering methodologies to scale up our squalene manufacturing capabilities for marketplace commercializationand twoif any of our novel triterpenes proves efficacious in stimulating antibody titerswe would need to pursue additional pre clinical evaluations of their safety and potential for inciting undesirable inflammatory responses PROJECT NARRATIVE Vaccine adjuvants play a special role in the development of adaptive immunological responses because they stimulate more robust titers of antibodies without inciting undue inflammationAlthough triterpene based adjuvants are recognized for their efficacy in stimulating desirable immune responselimiting sources of squalene and squalene analogs have impeded use and development of these oil in water adjuvantsWe will provide equivalency testing of new Synthetic Biology generated triterpenespaving the way for scale up process engineering towards commercialization and providing the justification for advanced pre clinicalsafety evaluations