Additional adjuvants

In addition to the immunostimulatory substances discussed above, the adjuvanticity of a variety of other substances is also being appraised. These include saponins, liposomes and ISCOMs.

Saponins are a family of glycosides (sugar derivatives) widely distributed in plants. Each saponin consists of a sugar moiety bound to a 'sapogenin' (either a steroid or a triterpene). The immunostimulatory properties of the saponin fraction isolated from the bark of Quillaja (a tree) has been long recognized. Quil A (which consists of a mixture of related saponins) is used as an adjuvant in selected veterinary vaccines. However, its haemolytic potential precludes its use in human vaccines. Research efforts continue in an attempt to identify individual saponins (or derivatives thereof) that would make safe and effective adjuvants for use in human medicine.

Liposomes are membrane-based supramolecular particles that consist of a number of concentric lipid membrane bilayers separated by aqueous compartments (Figure 13.15). They were developed initially as carriers for therapeutic drugs. Initially, the bilayers were almost exclusively phospholipid based. More recently, non-phospholipid-based liposomes have been developed.

The adjuvanticity of liposomes depends upon their composition, number of layers and charge characteristics. They act as effective adjuvants for both protein- and carbohydrate-based antigens and help stimulate both B- and T-cell responses. Their likely mode of action includes depot formation, but they also possibly increase/enhance antigen presentation to macrophages. The exact molecular mechanism(s) by which they stimulate a T-cell response remains to be elucidated,

Figure 13.15 Generalized liposome structure. Refer to text for details

but it appears to be associated with their hydrophobicity. Liposomes are likely to gain more widespread use as adjuvants when technical difficulties, associated with their stability and consistent/ reproducible production, are resolved.

ISCOMs are stable (non-covalent) complexes composed of a mixture of Quil A, cholesterol and (an amphipathic) antigen. ISCOMs stimulate both humoral and cellular immune responses and have been used in the production of some veterinary vaccines. Their use in humans, however, has not been licensed so far, mainly due to safety concerns relating to the Quil A component.

In summary, therefore, a whole range of adjuvants have thus far been identified/developed. Problems of toxicity have precluded the use of many of these adjuvants (particularly in humans). However, research efforts continue in an attempt to develop the next generation of safe and, hopefully, even more effective vaccine adjuvants.

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