Clinical use of DNA vaccines

Abstract

Owing to their unique advantages in simplicity, safety, scalability, and possibility of repeated administrations, DNA vaccines represent an appealing and competitive immunization approach for a wide array of conditions, including but not limited to infectious diseases and cancer immunotherapy. Despite the exciting efficacy observed in preclinical studies, DNA vaccines have faced challenges in inducing strong immune responses in humans. This unexpected poor immunogenicity has severely hampered the translation of DNA vaccines from investigational medications to licensed products. To overcome this obstacle, tremendous efforts have been made to improve antigen expression and enhance immunogenicity. Among these endeavors, in vivo DNA electroporation (EP) has proved to be a breakthrough technology capable of mediating efficient DNA uptake and resulting in enhanced antigen expression and vaccine immunogenicity. EP-mediated DNA delivery has become one of the major platforms used in clinical trials to evaluate DNA vaccines in humans. In this chapter, in addition to EP delivery, other progress made in DNA vaccine development including plasmid optimization, antigen design, and immunologic adjuvants is also reviewed. Finally, the use of DNA vaccines in the context of clinical trials for infectious diseases and cancer immunotherapy is summarized. Specifically, the strategies that allow DNA vaccines to overcome antigenic diversity for viral infection and break immune tolerance for cancer therapy are explored. Based on the advantages of DNA vaccines and the immense progress, led by the electroporation-mediated vaccine delivery, DNA vaccines appear to have the potential to fundamentally transform the vaccine field, providing important benefits for preventing and curing diseases.