Rational design of vaccines: learning from immune evasion mechanisms of persistent viruses and tumors.

The induction of adaptive immunity and prevention of tolerance is a critical component of vaccination and immunotherapy in order to prevent pathogen-related diseases and to eradicate malignant cells. Although many acute infections can be controlled by vaccination, the development of prophylactic and therapeutic vaccines against persistent viruses and tumors remains challenging. The diverse immune evasion strategies used by persistent DNA viruses such as herpesviruses contribute directly to their persistence and escape from immune control. Intriguingly, many tumors have also developed escape mechanisms to dismantle similar aspects of the host's immune system. Analogous targets of immune evasion mechanisms comprise suppression of antigen presentation and T cell costimulatory pathways, induction of immunosuppressive cytokines, and obstruction of interferon and chemokine functions, which emphasizes them not only as critical elements of T cell activation pathways but also as the potential "Achilles' heels" of the host immune system. The insight that immune evasion by viruses and tumors targets analogous host immune pathways might lead to cross-pollination of the viral and tumor immunology research fields, which could lead to new perspectives and appreciation of the intricacies and subtleties that arise from the merging of these fields. Accordingly, a rational and combinatorial manipulation of immune evasion pathways and their targets should aid in the development of safer and more effective vaccine strategies and immunotherapies for a wide range of infections and malignancies.