Development of VesiVax Carbohydrate Conjugation Chemistry

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DESCRIPTION: In response to PA-10-150, we will test the hypothesis that the VesiVax(R) Conjugatable Adjuvant Lipid Vesicle (CALV) platform can provide an efficient method to develop carbohydrate conjugate vaccines that stimulates superior immune responses to unconjugated carbohydrate antigens and also provides more flexibility to control the immune response to carbohydrate antigens over currently employed conjugate vaccine technologies. To demonstrate the utility of the VesiVax(R) CALV platform for this purpose, we propose to develop a polysaccharide conjugation technology with the commercialization goal of producing an easy-to-use modification to the VesiVax(R) CALV line of products. It is anticipated that successful execution of this project will provide a new tool that will enable immunologists and vaccinologists to evaluate their carbohydrate antigens of interest. Polysaccharides are emerging as promising vaccine targets for a variety of pathogens including viruses, bacteria, fungi, and cancers. In this SBIR Phase I application, we will develop a simple carbohydrate conjugation method that couples polysaccharide antigens to free amines on either a protein scaffold or liposomes containing lipid amines. Specifically, using the capsular polysaccharide Vi from Salmonella enterica (typhi) as our model carbohydrate antigen, we will couple Vi directly to VesiVax(R) CALVs containing a Toll-like Receptor 4 (TLR4) agonist or to a protein scaffold based on the mutant of diphtheria toxin known as CRM197 engineered to have a C-terminal cysteine residue (CRM197-Cys). The Vi-CRM197-Cys will then be conjugated to the VesiVax(R) CALVs. The VesiVax(R) Vi CALV conjugates containing the TLR4 agonist will then be tested in a mouse model of immunization to demonstrate the utility of the proposed approach.