Page 800 - Veterinary Immunology, 10th Edition

is possible to purify those with potent adjuvant activity and
VetBooks.ir minimal toxicity. Highly purified saponins are used in humans.

Saponin-based adjuvants selectively stimulate Th1 responses since
they direct antigens into endogenous processing pathways and

enhance IFN-γ release by dendritic cells. The saponins activate
inflammasomes. Saponin is also employed as an adjuvant for foot-
and-mouth disease vaccines and recombinant feline leukemia
vaccine. Toxic saponin mixtures are used in anthrax vaccines,

where they destroy tissue at the site of injection so that the anthrax
spores may germinate. Micelles may be constructed using protein
antigens and a complex saponin mixture called Quil-A. Immune
stimulating complexes (ISCOMs) are stable constructs containing

cholesterol, phospholipid, saponin, and antigen. ISCOMs are
effective adjuvants with few adverse side effects. They are highly
effective in targeting antigens to the professional antigen-
processing cells, whereas the saponin activates these cells and

promotes cytokine production and the expression of co-stimulatory
molecules. Depending on the antigen employed, ISCOMs can
stimulate either Th1 or Th2 responses.

Water-in-Oil Emulsions

One method of forming a slow-release antigen depot is to
incorporate the antigen in a water-in-oil emulsion (droplets of the
aqueous phase plus a surfactant such as Tween, Span, or lecithin

emulsified in an oil phase). A light mineral oil stimulates a local,
chronic inflammatory response, and as a result, a granuloma or
abscess forms around the site of the inoculum. The antigen is
slowly leached from the aqueous phase of the emulsion. These
depot adjuvants may cause significant tissue irritation and

destruction. Mineral oils are especially irritating. Nonmineral oils,
although less irritating, are also less effective. Tissue damage
induced by adjuvants may also promote immunity since the

DAMPs generated by inflammation and cell necrosis stimulate both
dendritic cells and macrophages. Adjuvants with significant irritant
activity are not, however, acceptable in modern vaccines, and it is
essential to reduce this irritation while retaining adjuvant
effectiveness. In humans, squalene based oil-in-water emulsions

800