Advisor(s)
Pengfei Wang
Committee Member(s)
Allan Zajac
Jianmei Leavenworth
Jun Zhang
Sadanandan Velu
School
College of Arts and Sciences
Document Type
Dissertation
Department (new version)
Chemistry
Date of Award
1-7-2025
Abstract
Vaccine adjuvants are indispensable substances that help induce a fast, potent, and durable immune response when administered with vaccine antigens. Among the FDA-approved vaccine adjuvants for human use, three of the most recently approved ones contain saponin adjuvant QS-21. To address QS-21’s inherent drawbacks, we investigated the adjuvant activity of a series of saponin-based semisynthetic vaccine adjuvants, including VSA-1 and VSA-2, prepared from natural Momordica saponins I and II in one-step. The natural saponins precursors are isolated from the widely available and inexpensive seeds of Momordica cochinchinensis SPRENG. In general, VSA adjuvants can enhance both humoral and cellular immune responses with lower toxicity and greater accessibility than QS-21. In a head-to-head comparison, VSA adjuvants’ immunostimulatory activity in enhancing the immune responses induced by the clinical glycoconjugate pneumococcal vaccine PCV13 is compared with QS-21. PCVs have effectively reduced pneumococcal diseases; however, traditional alum-adjuvanted PCVs have limitations. To improve the efficacy of new pneumococcal glycoconjugate vaccines, we focused on evaluating VSA adjuvants in alum-free pneumococcal glycoconjugates. Since the immunogenicity of glycoconjugates is significantly influenced by their conjugation methods, we further investigated the adjuvant activity of VSAs in conjunction with pneumococcal glycoconjugates prepared with different synthetic approaches. iv Moreover, we designed, synthesized, and evaluated new analogues of VSA-2 to explore structure-activity relationships (SAR), investigating the impact of terminal functionalization of side chain on adjuvanticity. Further investigation suggests that maintaining the intact VSA-2 molecular framework, substitutions at the terminal benzyl group of the side chain largely preserve the saponins’ ability to enhance antigen-specific humoral (IgG1 and IgG2a) and cellular responses. Overall, this study demonstrates that VSA adjuvants have the potential to help induce robust and long-lasting antigen-specific immune responses and confirms that derivatization at C3 glucuronic acid is a viable way to obtain new saponin adjuvants with desired properties and structurally defined molecular probes for mechanistic studies.
ProQuest ID
Recommended Citation
Kim, Hyunjung, "Development Of Momordica Saponin-Based Vaccine Adjuvants" (2025). All ETDs from UAB. 7250.
https://digitalcommons.library.uab.edu/etd-collection/7250
