Aluminium-based adjuvants

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,... 

A number of different adjuvant preparations have been developed (Table 13.13). Most preparations also display some associated toxicity and, as a general rule, the greater the product s adjuvanticity, the more toxic it is likely to be. A few different adjuvants may be used in veterinary medicine however (for safety reasons), aluminium-based products are the only adjuvants routinely used in human medicine. Application of many of the aggressive adjuvant materials is reserved for selected experimentation purposes in animals. 

Table 13.13 Overview of the adjuvant preparations that have been developed to date, or are under investigation. Of these, aluminium-based substances are the only adjuvants used to any significant degree in humans. Calcium phosphate and oil emulsions find very limited application in human medicine...

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 pg of protein. 

Various additional oil-based adjuvants have subsequently been developed. Adjuvant 65, for example, consists of 86% peanut oil, 10% Arlacel A and 4% aluminium monostearate (as a stabilizer). Unlike mineral oil, peanut oil is composed largely of triglycerides, which are readily metabolized by the body. Although adjuvant 65 was initially proved safe and effective in humans, it displayed less adjuventicity than FIA. Its use was largely discontinued, mainly due to the presence in its formulation of Arlacel A. 

In children aged 15-16 years receiving routine reinforcement tetanus immunization, adsorbed vaccine caused more intense and more frequent local reactions than did plain tetanus toxoid, and a higher incidence of pjrexia. The incidence of swelling and erythema at the inoculation site increased with serum antitoxin titre at the time of administration, whereas pain and tenderness were related to the presence of the aluminium hydroxide adjuvant (17). Based on similar experiences it has been widely recommended that plain and not adsorbed tetanus toxoid should be used when reinforcement of immunity to tetanus alone is desired. 

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