# Development of Structurally Defined Synthetic Vaccine Adjuvants

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $284,294

## Abstract

Adjuvants are substances that enhance the ability of a vaccine to elicit strong and durable immune
responses to specific antigens. They are a key factor in developing subunit vaccines, and are in urgent need
and a priority for vaccine research. Despite recent progress, developing subunit vaccines is still bottlenecked
by the lack of safe and effective adjuvants. Discovery of novel adjuvants has emerged as a critical frontline
effort in vaccine research. Saponin immune adjuvants, especially the extracts from the Quillaja Saponaria (QS)
Molina tree bark, show promising adjuvant activity and are promising leads in developing structurally and
compositionally defined synthetic vaccine adjuvants. Among the only four purified and characterized
components of the complex tree bark extracts, the component QS-21 is one of the most sought-after human
vaccine adjuvants and has been evaluated in over 100 clinical trials of vaccines against cancers and various
infectious diseases. It is also a key component of the new adjuvant systems (e.g., AS01 and AS15) being
tested in over 20 current clinical trials by the pharmaceutical industry. However, naturally occurring QS
adjuvants have inherent drawbacks such as chemical instability, limited supply, difficult and low-yielding
purification, and dose-limiting toxicity, which are the serious hurdles to their wider clinical use. In spite of recent
efforts and progress in circumventing the limitations of QS-21, there remains an imperative need of structurally
defined and homogeneous QS saponin-based adjuvants with enhanced adjuvant activity, reduced toxicity,
simplified formulation, and much improved chemical stability and synthetic accessibility. Chemical synthesis is
currently the only viable way to access the variety of structurally defined unnatural QS saponins analogs in a
sufficient amount for adjuvant screenings and potential clinical application. In this application, we will focus on
the design, synthesis and immunological evaluations of new QS analogs.
Specific aim 1: To synthesize and evaluate QS saponin-based adjuvants with a side chain incorporated in the
west wing glucuronic acid unit.
Specific aim 2: To synthesize and evaluate QS saponin-based adjuvants with a galacturonic acid unit in place
of the east wing native fucose unit for easy side chain attachment.
Specific aim 3: To evaluate the QS saponin-based synthetic adjuvants.

## Key facts

- **NIH application ID:** 9838239
- **Project number:** 5R01GM120159-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Pengfei Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $284,294
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838239

## Citation

> US National Institutes of Health, RePORTER application 9838239, Development of Structurally Defined Synthetic Vaccine Adjuvants (5R01GM120159-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9838239. Licensed CC0.

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