**2.5.3 Aluminium-based compounds**

Aluminium salt adjuvants (aluminium hydroxide, aluminium phosphate) are generally used in combination with protein antigens as they form a precipitated or adsorbed vaccine. An efficient, safe and well tolerated adjuvant in humans is aluminium hydroxide (Alum). It has been approved for clinical use. Although traditionally thought to function primarily by forming a long-lasting depot for antigen and by promoting their uptake by APCs, it is now clear that innate immune stimulation plays a primary role in the adjuvant activity of alum (Lambrecht et al. 2009). Aluminium hydroxide is used primarily to enhance antibody production and does not utilize TLR for its function in vivo (Gavin et al. 2006).This adjuvant induces a Th-2 biased immune response in mice whereas in humans it stimulates also a Th-1 type immunity. *In vitro* studies demonstrated that Alum can activate the inflammosome pathway to produce IL1-β (Li et al. 2007).

Recently, aluminium hydroxide has been also shown to work well in DNA vaccination in pre-clinical models (Kenney and Edelman 2003). However, the enhancing effect of aluminium hydroxide on the immune response elicited by DNA vaccines, is not related to the levels of antigen expression. Rather, it seems to affect antigen after *in vivo* expression, suggesting the adjuvanticity of this substance is strictly related to the antigen delivery mechanism (Ulmer et al. 1999).
