Optimization of VesiVax® Lipidated Tucaresol Formulations

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 DESCRIPTION (provided by applicant): There is a significant interest and need for developing new immunostimulatory adjuvant molecules that stimulate potent immune responses. To date, the only immunostimulatory adjuvant molecule that has been approved for human use is the Toll-like Receptor (TLR) 4 agonist, monophosphoryl lipid A (MPL). Other immunostimulatory adjuvant molecules such as poly I:C, a synthetic double stranded RNA mimic (TLR3), resiquimod, a synthetic single stranded RNA mimic (TLR7/8) or CpG, a DNA oligonucleotide (TLR9), have been in clinical development for a number of disease indications. A new class of immunostimulatory adjuvant molecules, cyclic dinucleotides (CDNs), have recently been shown to exert potent immunostimulatory properties through activation of an internal receptor called the STimulator of INterferon Genes (STING). In this project, we propose to optimize a small molecule immunostimulatory adjuvant, tucaresol, which we have synthesized with a "lipid tail" to facilitate formulation in the VesiVax(r) vaccine and adjuvant platform technology. We will synthesize lipidated tucaresol (LT) derivatives and prepare VesiVax(r) LT formulations with a model recombinant protein antigen (i.e., gD3PEPcD-HD) which we have shown to provide protective immune responses in our well-characterized mouse model of intravaginal HSV2 challenge.