Adjuvants

To maximize the effectiveness of vaccines, especially those containing killed organisms, adjuvants are commonly added. Adjuvants can greatly enhance the body’s response to vaccines and are essential if longterm memory is to be established against soluble antigens. Adjuvants work in 1 of 3 ways: 1) depot adjuvants that protect antigens from rapid degradation and thus prolong immune responses, 2) particles that effectively deliver antigen to antigen-presenting cells, and 3) molecules that stimulate immune responses by mechanisms such as signaling through toll-like receptors.

Depot adjuvants delay the elimination of antigens and thus permit an immune response to last longer. Examples include aluminum salts such as aluminum hydroxide, aluminum phosphate, and aluminum potassium sulfate (alum). Some depot adjuvants incorporate the antigen in a water-in-oil emulsion. These depot adjuvants can cause significant tissue irritation and destruction. Mineral oils are especially irritating. Non-mineral oils, while less irritating, are also less effective and are now more widely used.

Particulate adjuvants include emulsions, microparticles, iscoms, and liposomes. All are designed to deliver antigen efficiently to antigen-presenting cells. They commonly are of similar size to bacteria and are readily endocytosed by antigen-presenting cells. They are not yet widely used in veterinary vaccines due to complexities in the manufacturing process.

Immunostimulatory adjuvants promote cytokine production by activating antigen-processing cells. They include lipopolysaccharides, killed anaerobic corynebacteria (especially Propionibacterium acnes and Bordetella pertussis ), microbial cytidylate-phosphate-guanylate DNA, and saponins. Very powerful adjuvants can be constructed by combining a particulate or depot adjuvant with an immunostimulatory agent.