ArticleThe Journal of biological chemistry2016
Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 2 of them syntheses that pooled it.
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Who cites it
132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Immunological Activity of Vaccine Systems Containing Liposomal Nanocarriers against Protozoan-induced Diseases: A Systematic Review.Current medicinal chemistry · 2025Pooled it
- Controlling timing and location in vaccines.Advanced drug delivery reviews · 2020Pooled it
- Toxicological evaluation of a synthetic QS-21 adjuvant in a tuberculosis vaccine candidate-Demonstrating safety and immunological equivalence to natural reference.Human vaccines & immunotherapeutics · 2026Article
- Immunostimulant-integrated acrylate nanocomposite adjuvants potentiate foot-and-mouth disease vaccine efficacy.International journal of pharmaceutics: X · 2026Article
- Trained Immunity in Childhood Vaccination.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- Advances in the heterologous biosynthesis of QS saponins: a review.Microbial cell factories · 2026Review
- Immunogenicity ofVaccines · 2026Article
- Vaccine Adjuvants and Delivery Systems: A Comprehensive Review.International journal of molecular sciences · 2026Review
- Superior protection against tuberculosis using heterologous mRNA nanoadjuvant vaccines.NPJ vaccines · 2026Article
- Cooperative supramolecular integration of QS-21 into polymeric micelles as a tunable nanoadjuvant platform for subunit vaccines.RSC advances · 2026Article
- Quillaja saponaria fraction QS-18 as an adjuvant for liposomal seasonal influenza vaccines.NPJ vaccines · 2026Article
- Review
- Therapeutic Effects ofInternational journal of molecular sciences · 2026Article
- Article
- Aluminum adjuvants differentially induce IL-1β release in vitro yet share NLRP3 inflammasome-independent adjuvant effects in vivo.Scientific reports · 2026Article
- Adjuvants MPLA and SMNP induce antiviral immunity and indirectly revert HIV-1 latency.PloS one · 2026Article
- Structure and immunological activity of QS-21 variant fromFrontiers in immunology · 2026Article
- Dissecting the mechanism of action of the adjuvant system AS01 in human immune cells: synergy of QS-21 and monophosphoryl lipid A and role of type I interferons.Frontiers in immunology · 2026Article
- Poly(allylamine)/tripolyphosphate nanocomplex coacervate as a NLRP3-dependent systemic and mucosal adjuvant for vaccines.Frontiers in immunology · 2026Article
- Vaxjo 2.0: An ontology- and large language model-powered knowledge base of vaccine adjuvants and mechanisms.Frontiers in cellular and infection microbiology · 2026Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Many immunostimulants act as vaccine adjuvants via activation of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. However, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-dependent IL-1β and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4-agonist adjuvant monophosphoryl lipid A. Furthermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1β/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS-21 as part of a heterogeneous mixture of saponins also induced IL-1β in an NLRP3-dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immunized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen-specific responses in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.