{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:41:22Z","timestamp":1791848482448,"version":"4.3.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    QS-21 is a triterpenoid saponin adjuvant component widely used in human vaccines, but its commercial supply is limited because it is sourced almost exclusively from the bark of mature\n                    <jats:italic>Quillaja saponaria<\/jats:italic>\n                    trees in Chile. In this study, we report the identification, isolation, as well as structural and immunological characterization of QS-21-Rhamnose (QS-21-Rha), a naturally occurring structural variant that predominates in the leaves and twigs of young\n                    <jats:italic>Q. saponaria<\/jats:italic>\n                    shrubs cultivated in California. Analytical profiling showed that QS-21-Rha represents more than 95% of QS-21 variants in the aerial biomass. High-resolution MS\/MS and NMR spectroscopy confirmed that QS-21-Rha differs from QS-21 by the C3 terminal rhamnose substitution of xylose. Both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies demonstrated that QS-21-Rha elicits strong adaptive immune responses, notably robust CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation with immunostimulatory potency comparable to, and exceeding, that of traditionally bark-derived QS-21. From a production standpoint, aerial tissues provide a renewable and higher-yielding source where 1 kg of QS-21 can be obtained from pruning 200 young shrubs, compared with ~1,700 kg of bark, which is equivalent to debarking 100\u2013120 mature trees. These results establish QS-21-Rha as a chemically defined, immunologically active, and more sustainable vaccine adjuvant candidate to potentially address both supply-chain resilience and global vaccine access.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1771912","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:30:05Z","timestamp":1773034205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Structure and immunological activity of QS-21 variant from Quillaja saponaria aerial biomass"],"prefix":"10.3389","volume":"17","author":[{"given":"Ricardo","family":"San Mart\u00edn","sequence":"first","affiliation":[{"name":"Sutardja Center for Entrepreneurship and Technology, College of Engineering, University of California, Berkeley","place":["Berkeley, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute","place":["La Jolla, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute","place":["La Jolla, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Fox","sequence":"additional","affiliation":[{"name":"Access to Advanced Health Institute (AAHI)","place":["Seattle, WA, United States"]},{"name":"Department of Biological Engineering, College of Engineering, Utah State University","place":["Logan, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Ravi","family":"Iyer","sequence":"additional","affiliation":[{"name":"Access to Advanced Health Institute (AAHI)","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raodoh","family":"Mohamath","sequence":"additional","affiliation":[{"name":"Access to Advanced Health Institute (AAHI)","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabi","family":"Ramer-Denisoff","sequence":"additional","affiliation":[{"name":"Access to Advanced Health Institute (AAHI)","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kinsey","sequence":"additional","affiliation":[{"name":"Access to Advanced Health Institute (AAHI)","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Guderian","sequence":"additional","affiliation":[{"name":"Access to Advanced Health 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton","family":"Radke","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, College of Chemistry, University of California, Berkeley","place":["Berkeley, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.146.2.431","article-title":"Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex","volume":"146","author":"Kensil","year":"1991","journal-title":"J Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02866497","article-title":"Industrial uses and sustainable supply of Quillaja saponaria (Rosaceae) saponins","volume":"53","author":"Martin","year":"1999","journal-title":"Econ Bot"},{"key":"B3","article-title":"QS-21 and QS-7: 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