Yuzhong Liu, PhD
Biosynthesis of Safer and More Effective Vaccine Adjuvants
Abstract
Vaccine adjuvants are critical for enhancing immune responses, yet only a few are clinically approved. QS-21, the only saponin adjuvant is potent but limited by scarcity and dose-limiting toxicity. Other close analogs offer similar potency with reduced cytotoxicity, making them promising next-generation adjuvant candidates. However, their structural complexity and low abundance have prevented systematic study. This project applies in vivo chemical directed evolution to the reconstituted these pathways in engineered microbes, enabling diversification of glycosylation and acylation modules. Libraries of saponin analogs will be generated and evaluated using high-throughput functional assays to directly couple structural diversity to immune outcomes. These studies will define the structural basis for saponins’ improved safety, yield optimized adjuvant candidates, and establish a generalizable platform for function-driven evolution of natural products with broad applications in drug discovery.
This award provides critical support for our early efforts to build a biosynthetic platform for drug discovery and development. By harnessing nature’s chemistry, we can access complex structures that are difficult to produce using traditional synthetic approaches.
