Optimization of VesiVax® Lipidated Tucaresol Formulations

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 agonist monophosphoryl lipid A MPL Other immunostimulatory adjuvant molecules such as poly I C a synthetic double stranded RNA mimic TLR resiquimod a synthetic single stranded RNA mimic TLR or CpG a DNA oligonucleotide TLR 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 andquot lipid tailandquot 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 gD PEPcD HD which we have shown to provide protective immune responses in our well characterized mouse model of intravaginal HSV challenge PUBLIC HEALTH RELEVANCE This project could exert a significant impact on the field of vaccine and adjuvant research by identifying an optimal lipid derivative of tucaresol LT This would be highly valuable since the ability to match a particular protein or peptide antigen with an appropriate adjuvant molecule to generate an optimal immune response represents an advance over current strategies for protein or peptide vaccine development In addition the fine control o the concentrations of the lipids and LT molecules to be synthesized in this project combined with the ability to manipulate the ratio of these components with a target protein antigen to maximize the immune response cannot be easily achieved with any other adjuvant system The development of new LT formulations using the VesiVax technology platform is intended to make the development of potent subunit vaccines much easier and hence will be of great benefit to public health