Adjuvant technology

Administration of many vaccines on their own stimulates a poor host immunological response. This is particularly true of the more recently developed subunit vaccines. An adjuvant is defined as any material that enhances the cellular and/or humoral immune response to an antigen. Adjuvants thus generally elicit an earlier, more potent and longer-lasting, immunological reaction against co-administered antigen. In addition, the use of adjuvants can often facilitate administration of reduced quantities of antigen to achieve an adequate immunological response. This implies consequent economic savings, as vaccines (particularly subunit and vector vaccines) are far more expensive to produce than the adjuvant.

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. An ideal adjuvant should display several specific characteristics. These include:

• safety (no unacceptable local/systemic responses);

• elicit protective immunity, even against weak immunogens;

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

Mineral compounds

Bacterial products

Oil-based emulsions

Saponins Liposomes

Immunostimulatory complexes (ISCOMs) Some cytokines

Aluminium phosphate (AlPO4) Aluminium hydroxide (Al(OH)3) Alum (AlK(SO4)2.12H2O) Calcium phosphate (CaPO4) Mycobacterial species

Mycobacterial components, e.g. trehalose dimycolate (TDM), muramyl dipeptide (MDP) Corynebacterium species B. pertussis LPS

Freund's complete/incomplete adjuvant (FCA/FIA) Starch oil Quil A

• be chemically defined (facilitates consistent manufacture and QC testing);

• be effective in infants/young children;

• yield stable formulation with antigen;

• be biodegradable;

• be non-immunogenic itself.

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