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Towards an understanding of the adjuvant action of aluminium
Open accessAbstract
The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work.
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“The mechanism of action of aluminium salts (alum), although extensively used as an adjuvant for more than 80 years, remains incompletely understood15”
From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [15]
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Cites
Mosmann, T. R., Cherwinski, H. M., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.7.2348 · Cited by 7,553
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008) · Science · doi:10.1126/science.1156995 · Cited by 2,658 · cited 1×
“Related reports have shown that other particulate materials, such as silica, asbestos and MSU crystals, also act through the NLRP3 inflammasome to produce IL-1&beta”
How dying cells alert the immune system to danger
Kono, H., & Rock, K. L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2215 · Cited by 1,737
Molecular identification of a danger signal that alerts the immune system to dying cells
Shi, Y., Evans, J. E., & Rock, K. L. (2003) · Nature · doi:10.1038/nature01991 · Cited by 1,684
Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
Eisenbarth, S. C., Colegio, O. R., O’Connor, W., Sutterwala, F. S., & Flavell, R. A. (2008) · Nature · doi:10.1038/nature06939 · Cited by 1,542
Toll-like receptors control activation of adaptive immune responses
Schnare, M., Barton, G. M., Czopik, A. K., Takeda, K., Akira, S., & Medzhitov, R. M. (2001) · Nature Immunology · doi:10.1038/ni712 · Cited by 1,364
Disruption of the murine IL-4 gene blocks Th2 cytokine responses
Köpf, M., Gros, G. S. L., Bachmann, M. F., Lamers, M. C., Bluethmann, H., & Köhler, G. (1993) · Nature · doi:10.1038/362245a0 · Cited by 1,202
Kool, M., Soullié, T., van Nimwegen, M., Willart, M. A. M., Muskens, F., Jung, S., Hoogsteden, H. C., Hammad, H., & Lambrecht, B. N. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071087 · Cited by 1,014
Research works printed but not linked: 1
- Ramon, G. Sur le pouvoir floculant et sur les proprietes immunisantes d'une toxine diphtherique rendue anatoxique. C. R. Hebd. Seances Acad. Sci. 177, 1338–1340 (1923).
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Janssen, E., Shulman, A. I., & Sundel, R. P. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4377-0271-2.00014-6
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Das, S., Tenaglia, B. M., Riley, D. V., Speed, S., Baracco, L., Gardner, F. M., Varisco, D. J., Yang, H., Nijhuis, H., Kerstetter, L. J., et al. (2026) · Vaccine · doi:10.1016/j.vaccine.2026.128774
Zhang, W. T., Wei, C., 黄海涛, Wang, X., Xie, Z., Wu, Y., Wang, F., Huang, L., Wang, X., Sui, X., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1874647
Wang, J., He, Y., Liu, J., Ru, Q., Huang, Y., Quan, W., Mu, H., Du, H., & Gou, J. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.153412
Yan, Y., Li, Y., Mei, W., Li, Y., Wang, Q., Li, H., Lu, L., & Jiang, S. (2026) · Virologica Sinica · doi:10.1016/j.virs.2026.07.006
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Jin, P., Quan, Y., Gao, X., Wei, M., Cao, X., Pan, H., Shen, H., Zhao, L., Xu, Q., Wang, Z., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76313-w
Fox, N., Trausch, J. J., Yarovoi, H., Stiving, A. Q., Bowman, A. M., Lauro, M. L., Liu, Y., Eddins, M. J., Loughney, J. W., Todd, M., et al. (2026) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2026.104461
Chen, H., Wang, R., Zhang, Z., Yang, Z., Wen, Z., Li, L., Liu, Z., Fan, D., Xu, Y., Li, M., et al. (2026) · ACS Nano · doi:10.1021/acsnano.6c09358
Xie, M., Wu, Q., Sheng, Y., Wu, W., & Lü, Y. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.127377
Wang, Z., Pu, D., Gu, Q., Luo, L., Wu, G., Ma, J., Yang, L., Li, Y., Dong, X., & Wu, M. (2026) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2026.125832
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Bürgel, P. H. (2015) · RIUnB Institutional Repository (University of Brasília) · doi:10.26512/2015.02.d.18230
Metadata
- Authors
- Marrack, P., McKee, A. S., & Munks, M. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Marrack, Philippa
- Venue
- Nature Reviews Immunology
- Published
- 2009-04
- Volume
- 9
- Issue
- 4
- Pages
- 287-293
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC3147301
- OpenAlex
- W1990954596
- Cited by
- 887
- References
- 63
- Citations by year
- 2026: 44 · 2025: 47 · 2024: 57 · 2023: 47 · 2022: 41 · 2021: 67 · 2020: 50 · 2019: 45 · 2018: 49 · 2017: 65 · 2016: 56 · 2015: 72 · 2014: 44 · 2013: 64 · 2012: 49
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (P01AI022295, R37AI018785)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- alum adjuvant, aluminum salts, vaccine adjuvants, adjuvant mechanisms, vaccine efficacy, immunogenicity
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adjuvants, Immunologic, Adsorption, Aluminum, Animals, Antibody Formation, Antigen-Presenting Cells, Antigens, Carrier Proteins, Cytoskeletal Proteins, Humans, Immunity, Cellular, Immunity, Innate, Aluminum Compounds, Models, Immunological, Caspase 1, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins
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