The immunobiology of aluminium adjuvants: how do they really work?
Abstract
Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.
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As an adjuvant, Al in vaccines induces local inflammation involving the NLRP3 inflammasome and NLRP3-independent pathways, where macrophages, B- and T-lymphocytes play important roles in enhancing antigen-specific immune responses and increasing inflammatory cytokine production.
“As an adjuvant, Al in vaccines induces local inflammation that involves the NLRP3 inflammasome and NLRP3-independent pathways where macrophages, B- and T-lymphocytes play important roles in enhancing antigen-specific immune responses and increasing inflammatory cytokine production (Exley et al., 2010; Hogenesch, 2013; Zlatkovic et al., 2013; He et al., 2015).”
From Aluminium toxicosis: a review of toxic actions and effects (2019) · cites this paper as Exley et al., 2010
Cites
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 · see citing works
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 · see citing works
Towards an understanding of the adjuvant action of aluminium
Marrack, P., McKee, A. S., & Munks, M. W. (2009) · Nature Reviews Immunology · doi:10.1038/nri2510 · Cited by 887 · see citing works
Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox
Rubartelli, A., & Lotze, M. T. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.08.004 · Cited by 614 · see citing works
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Aluminium toxicosis: a review of toxic actions and effects
Igbokwe, I. O., Igwenagu, E., & Igbokwe, N. A. (2019) · Interdisciplinary Toxicology · doi:10.2478/intox-2019-0007 · Cited by 395 · see citing works
“…involves the NLRP3 inflammasome and NLRP3independent pathways where macrophages, B- and T-lymphocytes play important roles in enhancing antigenspecific immune responses and increasing inflammatory cytokine production (Exley et al., 2010; Hogenesch, 2013; Zlatkovic et al., 2013; He et al., 2015).”
BackgroundExley, C. (2013) · Environ. Sci.: Processes Impacts · doi:10.1039/c3em00374d · Cited by 382 · see citing works
Self-citationAluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice
Pineton de Chambrun, G., Body-Malapel, M., Frey-Wagner, I., Djouina, M., Deknuydt, F., Atrott, K., Esquerre, N., Altare, F., Neut, C., Arrieta, M. C., et al. (2014) · Mucosal Immunology · doi:10.1038/mi.2013.78 · Cited by 108 · see citing works
- Authors
- Exley, C., Siesjö, P., & Eriksson, H.
- Affiliations
- Keele University (GB)
- Lund University (SE)
- Malmö University (SE)
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 31
- Issue
- 3
- Pages
- 103-109
- ISSN
- 1471-4906 (ISSN-L)
- OpenAlex
- W1982584872
- Cited by
- 184
- References
- 4
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 9 · 2023: 12 · 2022: 7 · 2021: 16 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 14 · 2016: 13 · 2015: 22 · 2014: 19 · 2013: 20 · 2012: 13
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Malmö University Publications (Malmö University) (submittedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- alum adjuvant, immunobiology, adjuvant mechanisms, vaccine potency, adjuvant safety, mass vaccination program
- MeSH terms
- Adenosine Triphosphate, Adjuvants, Immunologic, Aluminum Hydroxide, Animals, Antigen-Presenting Cells, B-Lymphocytes, Humans, Immunity, Innate, Inflammation, Oxidation-Reduction, Phagocytes, Phosphates, T-Lymphocytes, Vaccines, Reactive Oxygen Species, Aluminum Compounds, Magnesium Compounds, Models, Immunological, Muscle, Skeletal, Inflammation Mediators, Extracellular Fluid, Adaptive Immunity
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