Mineralbased adjuvants

A number of mineral-based substances display an adjuvant effect. Although calcium phosphate, calcium chloride and salts of various metals (e.g. zinc sulfate and cerium nitrate) display some effect, aluminium-based substances are by far the most potent. Most commonly employed are aluminium hydroxide and aluminium phosphate (Table 13.13). Their adjuvanticity, coupled to their proven safety, render them particularly valuable in the preparation of vaccines for young children. They have been incorporated into millions of doses of such vaccine products so far.

The principal method by which aluminium adjuvanted vaccines are prepared entails mixing the antigen in solution with a preformed aluminium phosphate (or hydroxide) precipitate under chemically defined conditions (e.g. of pH). Adsorption of the antigen to the aluminium-based gel ensues, with such preparations being generally termed 'aluminium-adsorbed vaccines'; 1 mg of aluminium hydroxide will usually adsorb in the order of 50-200 ^g of protein.

The major mode of action of such products appears to be depot formation at the site of injection. The antigen is only slowly released from the gel, ensuring its sustained exposure to immune surveillance. The aluminium compounds are also capable of activating complement. This can lead to a local inflammatory response, with consequent attraction of immunocompetent cells to the site of action.

Despite their popularity, aluminium-based adjuvants suffer from several drawbacks. They tend to stimulate only the humoral arm of the immune response effectively. They cannot be frozen or lyophylized, as either process promotes destruction of their gel-based structure. In addition, aluminium-based products display poor/no adjuvanticity when combined with some antigen (e.g. typhoid or Haemophilus influenzae type b capsular polysaccharides).

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