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Research showed that such preparations could be highly heterogenous, depending on which anions (such as bicarbonate, sulfate or phosphate) were present at the time of precipitation (e.g.

as buffer constituents or growth media residues in the antigen solution).

The size of the aluminium hydroxide particles is comparable to the size of microorganisms and is adequate for uptake by phagocytosis by APC.

Emphasis is placed on the important factors for antigen adsorption and on the latest work using gene-deficient mice in the research of the mechanism of aluminium adjuvants in terms of cytokine and T-cell subset stimulation.

Key references on the ability of aluminium adjuvants to stimulate Ig E and also in vivo clearing of aluminium adjuvants are discussed.

Vaccine preparations based on this approach are called aluminium-adsorbed vaccines in contrast to alum-precipitated vaccines.

Aluminium phosphate was introduced as an adjuvant somewhat later.

Adjuvant Department, Brenntag Biosector, DK-3600 Frederikssund, Denmark Correspondence: Dr EB Lindblad, Adjuvant Department, Brenntag Biosector, DK-3600 Frederikssund, Denmark.

Email: [email protected] ; Accepted 5 July 2004.

Particle size distributions of the aluminium gel particles can be obtained using, for example, laser diffraction analysis.

An example of this, obtained using Malvern equipment, is given in Figure 1.

The present review gives a short introduction to the pioneering research at the start of the use of aluminium compounds as adjuvants, including references on the chemistry of these compounds.

Analytical methods for identifying the most commonly used aluminium compounds, such as boehmite and aluminium hydroxyphosphate, are mentioned.

In 1946, Ericsson, shortly after, demonstrated that preformed aluminium phosphate, prepared from equimolar amounts of aluminium chloride and trisodium phosphate, acted as an adsorbant and was adjuvant active with diphtheria.