License to kill: Formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems.

Induction of CD8(+) T-cell responses is critical for the immunological control of a variety of diseases upon vaccination. Modern subunit vaccines are based on highly purified recombinant proteins. The high purity represents a major advancement in terms of vaccine safety compared to previous vaccination strategies with live attenuated or whole killed pathogens, but typically renders vaccine antigens poorly immunogenic and insufficient in mobilizing protective immunity. Adjuvants are therefore needed in vaccine formulations to enhance, direct and maintain the immune response to vaccine antigens. However, a weakness of many adjuvants is the lack of induction of CD8(+) T-cell responses against protein antigens, which are required for protection against challenging and difficult infectious diseases such as AIDS and for therapeutic cancer vaccination. Within the last decade, adjuvant systems that can induce CD8(+) T-cell responses have been developed and the first clinical trials demonstrating the clinical relevance of such formulations have been performed. This paper reviews the current status of lipid- and polymer-based particulate antigen delivery systems capable of stimulating CD8(+) T-cell immunity with special focus on mechanisms of priming and pharmaceutical requirements for optimal activation of cytotoxic T-lymphocytes that can kill virus-infected or abnormal (cancer) cells.