Targeting the skin for genetic immunization.

Abstract

One of the most promising applications of recent advances in gene therapy is the development of immunization strategies based on the delivery of antigen-encoding DNA. DNA-based vaccination, also referred to as genetic vaccination or polynucleotide vaccination, offers considerable promise for improvement over existing immunization strategies, and the skin offers unique potential as a target tissue for genetic vaccines. The expression of genetically introduced antigens in a cutaneous microenvironment rich in both professional antigen-presenting cells and accessory cells, which are capable of producing immunostimulatory cytokines, has the potential to overcome the historical limitations of vaccinology and immunotherapy. Though the precise molecular mechanisms of genetic immunization remain unclear, a general working model of the events through which antigen-encoding plasmids introduced into the skin initiate an immune response can be constructed. The finding that Langerhans cells can be transfected in vivo raises the exciting possibility that these migrating professional antigen-presenting cells can be genetically engineered in vivo. By designing strategies to codeliver genes encoding antigens with genes encoding immunoregulatory molecules to the same antigen-presenting cell, it may be possible to either induce or suppress antigen-specific immune responses in the host. Though many aspects of the biology of cutaneous DNA immunization remain unknown, the skin appears to offer unique potential for the application of advances in gene therapy to vaccination and genetic engineering of the immune response.