2. Academic Validation
  3. Developing a Next-Generation Vaccine Adjuvant System through Rational Design to Alleviate AS01 Adjuvant Deficiency

Developing a Next-Generation Vaccine Adjuvant System through Rational Design to Alleviate AS01 Adjuvant Deficiency

  • J Med Chem. 2026 Apr 9;69(7):8535-8547. doi: 10.1021/acs.jmedchem.6c00135.
Zhikuan Luo 1 2,  Shijun Zhou 1 2,  Hong Wang 1,  Wanwan Ge 3,  Zhongqi Liu 4,  Ming He 4,  Tao Zhong,  Yuping Wang 1,  Xiangtong Li 1,  Shaohua Wang 1,  Xiaolei Wang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Product Chemistry, Department of Chemistry and School of Pharmacy, Lanzhou University, Lanzhou 730000, P. R. China.
  • 2 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Lanzhou University, Chinese Academy of Agricultural Sciences, Lanzhou 730000, P. R. China.
  • 3 Translational Cancer Bioinformatics, Robert Bosch Center for Tumor Diseases, Stuttgart 70376, Germany.
  • 4 State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University, Kunming 650021, P. R. China.
PMID: 41855509 DOI: 10.1021/acs.jmedchem.6c00135
Abstract

Vaccine adjuvants play a crucial role in enhancing immunogenicity, with AS01 distinguishing itself due to its potent immunostimulatory properties. However, its broader application in vaccines is limited by several critical challenges, including the scarcity of QS-21, stringent storage requirements, and inherent toxicity. To address these challenges, the present study focuses on the development of novel nonliposomal Adjuvant systems, specifically BST01 and BST02, utilizing simplified QS-21 derivatives. The design of these new adjuvants aims to achieve cost-effective synthesis, reduced storage constraints, improved immunogenicity, and decreased hemolytic toxicity. The results show that BST01 and BST02, when coadministered with antigen, induce antibody titers comparable to those of AS01. Collectively, these findings demonstrate that BST01 and BST02 not only mitigate the limitations associated with AS01 but also represent promising candidates for next-generation vaccine adjuvants, demonstrating enhanced efficacy, improved practicality─particularly with respect to storage convenience, and increased safety.

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