{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:41:27Z","timestamp":1791848487898,"version":"4.3.4"},"reference-count":123,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM120159; AI099407"],"award-info":[{"award-number":["GM120159; AI099407"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Saponin adjuvants have been extensively studied for their use in veterinary and human vaccines. Among them, QS-21 stands out owing to its unique profile of immunostimulating activity, inducing a balanced Th1\/Th2 immunity, which is valuable to a broad scope of applications in combating various microbial pathogens, cancers, and other diseases. It has recently been approved for use in human vaccines as a key component of combination adjuvants, e.g., AS01b in Shingrix\u00ae for herpes zoster. Despite its usefulness in research and clinic, the cellular and molecular mechanisms of QS-21 and other saponin adjuvants are poorly understood. Extensive efforts have been devoted to studies for understanding the mechanisms of QS-21 in different formulations and in different combinations with other adjuvants, and to medicinal chemistry studies for gaining mechanistic insights and development of practical alternatives to QS-21 that can circumvent its inherent drawbacks. In this review, we briefly summarize the current understandings of the mechanism underlying QS-21\u2019s adjuvanticity and the encouraging results from recent structure-activity-relationship (SAR) studies.<\/jats:p>","DOI":"10.3390\/vaccines9030222","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:03:15Z","timestamp":1614920595000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Natural and Synthetic Saponins as Vaccine Adjuvants"],"prefix":"10.3390","volume":"9","author":[{"given":"Pengfei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/j.1365-3024.2009.01143.x","article-title":"The development of the RTS,S malaria vaccine candidate: Challenges and lessons","volume":"31","author":"Ballou","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1471-4159.2011.07458.x","article-title":"\u2018Clinical trials in Alzheimer\u2019s disease\u2019: Immunotherapy approaches","volume":"120","author":"Delrieu","year":"2012","journal-title":"J. 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