Designer adjuvants for enhancing the efficacy of infectious disease and cancer vaccines based on suppression of regulatory T cell induction

Live attenuated or inactivated bacteria and viruses have formed the basis of many successful vaccines, including those that have eliminated smallpox and have almost eliminated poliovirus. The whole virus or bacteria approach remains the most effective means of generating protective immunity by vaccination. However, these vaccines can be associated with mild to severe side effects, such as that observed with the whole cell pertussis vaccine. Furthermore, rare cases of vaccine-associated disease can result from reversion of an attenuated virus to the virulent form, such as that reported with the oral polio vaccine. Advances in genomics, molecular biology and immunology have now facilitated the identification, recombinant expression and immunological characterization of protective antigens from infectious organisms, permitting a more rational approach to vaccine design. Purified native or recombinant proteins or polysaccharides (linked to carrier proteins) now provide a much cleaner, safer and more immunologically defined alternative to live or killed whole cell vaccines. However, these subunit vaccines lack the danger signals required to activate innate immune responses and must therefore be delivered with potent adjuvants or delivery systems in order to generate protective adaptive immune responses.