Aluminium in Allergies and Allergen immunotherapy

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Abstract

Aluminium is a hot topic in the current debate. Exposure occurs due to environmental, dietary and intentional exposure to aluminium, such as in vaccines where it was introduced in 1926. In spite of the fact that it is a typical Th2 adjuvant, aluminium redirects the immune response in systemic allergen immunotherapy (SIT) upon prolonged immunization. SIT in the US, and SLIT in general, are at present non-adjuvanted therapies, but in Europe aluminium is used as adjuvant in most SIT preparations. It enhances the safety of SIT by local deposition of the allergen. Undesired properties of aluminium adjuvants comprise acute and chronic inflammation at the injection site, its Th2 immune stimulatory capacity, its accumulation besides biodistribution in the body. The adjuvant and safety profile of aluminium adjuvants in allergy vaccines are discussed, as well as the need for putting modern delivery systems and adjuvants on the fast track.

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Towards an understanding of the adjuvant action of aluminium.

Philippa Marrack, Amy S McKee, Michael W. Munks (2009)

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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Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity.

Nico van Rooijen, Michael W. Munks, Megan MacLeod … (2009)

To understand more about how the body recognizes alum we characterized the early innate and adaptive responses in mice injected with the adjuvant. Within hours of exposure, alum induces a type 2 innate response characterized by an influx of eosinophils, monocytes, neutrophils, DCs, NK cells and NKT cells. In addition, at least 13 cytokines and chemokines are produced within 4 h of injection including IL-1beta and IL-5. Optimal production of some of these, including IL-1beta, depends upon both macrophages and mast cells, whereas production of others, such as IL-5, depends on mast cells only, suggesting that both of these cell types can detect alum. Alum induces eosinophil accumulation partly through the production of mast cell derived IL-5 and histamine. Alum greatly enhances priming of endogenous CD4 and CD8 T cells independently of mast cells, macrophages, and of eosinophils. In addition, Ab levels and Th2 bias was similar in the absence of these cells. We found that the inflammation induced by alum was unchanged in caspase-1-deficient mice, which cannot produce IL-1beta. Furthermore, endogenous CD4 and CD8 T cell responses, Ab responses and the Th2 bias were also not impacted by the absence of caspase-1 or NLRP3. These data suggest that activation of the inflammasome and the type 2 innate response orchestrated by macrophages and mast cells in vivo are not required for adjuvant effect of alum on endogenous T and B cell responses.

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Alum adjuvant: some of the tricks of the oldest adjuvant.

N Lambrecht, Kaat Fierens, Mirjam Kool (2012)

Alum has been the most widely used adjuvant for over 80 years. Although there have been searches for alternative adjuvants, aluminium-containing adjuvants will continue to be used for many years due to their good track record of safety, low cost and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminium-containing adjuvants formulated under optimal conditions are the adjuvants of choice. There are also some limitations of aluminium-containing adjuvants, which include local reactions, augmentation of IgE antibody responses, ineffectiveness for some antigens and inability to augment cell-mediated immune responses, especially cytotoxic T-cell responses. In this review, we describe the current knowledge regarding the mechanisms (both cellular and molecular) by which alum employs its adjuvant effect, although the final mechanism is not yet well-defined. Furthermore, we discuss how alum's adjuvanticity could be improved.

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Author and article information

Contributors

Erika Jensen-Jarolim: Erika.jensen-jarolim@meduniwien.ac.at

Journal

Journal ID (nlm-ta): World Allergy Organ J

Journal ID (iso-abbrev): World Allergy Organ J

Title: The World Allergy Organization Journal

Publisher: BioMed Central (London )

ISSN (Electronic): 1939-4551

Publication date (Electronic): 28 February 2015

Publication date PMC-release: 28 February 2015

Publication date Collection: 2015

Volume: 8

Issue: 1

Electronic Location Identifier: 7

Affiliations

[ ]Comparative Medicine, Messerli Research Institute, The University of Vet. Medicine Vienna, the Medical University Vienna, and the University Vienna, Währinger G. 18-20, 1090 Vienna, Austria

[ ]Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria

Article

Publisher ID: 60

DOI: 10.1186/s40413-015-0060-5

PMC ID: 4348159

PubMed ID: 25780491

SO-VID: 7acd8c31-b1a4-4c13-9d29-707780690848

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 24 October 2014

Date accepted : 6 February 2015

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ScienceOpen disciplines: Immunology

Keywords: allergen,aluminium,adjuvant,allergen immunotherapy,th2

Data availability:

ScienceOpen disciplines: Immunology

Keywords: allergen, aluminium, adjuvant, allergen immunotherapy, th2

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Aluminium in Allergies and Allergen immunotherapy

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Cancer Immunotherapy

Most cited references 62

Towards an understanding of the adjuvant action of aluminium.

Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity.

Alum adjuvant: some of the tricks of the oldest adjuvant.

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