Recent advances in immunological adjuvants: the development of particulate antigen delivery systems.
New generation vaccines, including those based on recombinant proteins, are safer than traditional vaccines, but are less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. A number of potent immunostimulatory molecules obtained from bacterial cells or plants have been extensively evaluated as adjuvants. However, a number of these molecules have displayed significant toxicity, both in preclinical animal models and in human clinical trials. An alternative approach to the development of novel adjuvants involves the preparation of particulate antigen delivery systems of similar dimensions to natural pathogens. In the absence of additional immunostimulatory molecules, emulsion droplets and microparticles have been shown to be potent adjuvants for the induction of both humoral and cell-mediated immune responses following systemic administration. Moreover, particulate delivery systems have been shown to display an acceptable toxicity profile in a number of clinical trials. Particulate antigen delivery systems also have the potential to function as potent adjuvants following administration by mucosal routes, including oral and intranasal. An alternative approach to the mucosal delivery of vaccines involves the use of genetically detoxified mutant toxins, e.g., LT-K63, as mucosal adjuvants. The use of novel adjuvants and antigen delivery systems is likely to extend the use of vaccines into the area of therapeutics, involving the eradication of infectious diseases and cancers, or the amelioration of autoimmune disorders.
O'Hagan
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Chiron Corporation, 4560 Horton Street, Emeryville, CA 94704, USA. derek_o'hagan@cc.chiron.com