Biomedical Engineering Reference
In-Depth Information
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be non-pyrogenic;
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be chemically defi ned (facilitates consistent manufacture and QC testing);
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be effective in infants/young children;
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yield stable formulation with antigen;
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be biodegradable;
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be non-immunogenic itself.
13.5.1 Adjuvant mode of action
Adjuvants are a heterogeneous family of substances, both in terms of their chemical structure and
their mode of action. The observed adjuvanticity of any such substance may be due to one or more
of the following factors:
•
Depot formation of antigen. This results in the subsequent slow release of the antigen from the
site of injection, which, in turn, ensures its prolonged exposure to the immune system.
•
Enhanced antigen presentation to the cells of the immune system.
•
The direct induction of immunostimulatory substances, most notably interleukins and other cytokines.
13.5.2 Mineral-based 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 defi ned 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 µg 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 surveil-
lance. The aluminium compounds are also capable of activating complement. This can lead to a local
infl ammatory 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,
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