Optimize VSA Adjuvants through Medicinal Chemistry Study

Adjuvax Llc, Hoover AL

Investigators

Abstract

The goal of this project is to discovery semi-synthetic immunostimulatory saponins with distinct activity profiles to meet the need of various vaccine applications. Extensive SAR studies indicate that incorporating or removing a fatty side chain in the QS saponins to control cellular immunity can potentially be generalized to other saponin families. Therefore, the contractor will leverage the abundance and structural diversity of naturally occurring saponins and convert the weakly immunostimulatory natural saponins into more potent semi-synthetic counterparts through a simple chemical process and develop a focused library of natural and semi-synthetic saponins. The library will contain over 200 compounds, which will be screened in vitro using human PBMCs to identify promising hits. The top ~20 compounds will then undergo secondary screening and the most promising ~15 compounds will be evaluated in vivo using a mouse model and 2-3 final leads will be selected.