Antibodies, vaccines and adjuvants - Pharmaceutical Biotechnology: Concepts and Aapplications - page 417

Table 13.14 Some cell types activated upon administration of MDP. Activation
induces synthesis of a range of immunomodulatory cytokines by these (and other) cells

Cell types activated Macrophages

Mast cells
Polymorphonuclear leukocytes
Endothelial cells
Fibroblasts Platelets

Cytokines and other molecules induced IL-1

CSFs
Fibroblast activating factor
B-cell growth factor
Prostaglandins

A number of derivatives were synthesized in the hope of identifying a modifi ed form that re-
tained its adjuvanticity but displayed lesser toxicity. Some such derivatives, most notably threonyl-
MDP, muramyl tripeptide and murabutide, display some clinical promise in this regard.
Threonlyn-MDP, for example, has been included in the formulation known as Syntex adjuvant
formulation-1 (SAF-1). Animal studies suggest that this adjuvant is non-toxic and elicits a good
B- and T-cell response.
An additional bacterial component displaying appreciable adjuvanticity is the C. granulosum -
derived p40 particulate fraction. p40 is composed of fragments of cell wall peptidoglycan and
associated glycoproteins.

13.5.5 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 pre-
cludes its use in human vaccines. Research efforts continue in an attempt to identify indi-
vidual 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 concen-
tric lipid membrane bilayers separated by aqueous compartments (Figure 13.15). They were de-
veloped 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 anti-
gens and help stimulate both B- and T-cell responses. Their likely mode of action includes de-
pot 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,