DNA IMMUNIZATION TARGETING THE SKIN - MOLECULAR CONTROL OF ADAPTIVE IMMUNITY

DNA-based immunization represents a novel approach for vaccine develop ment. Recombinant DNA techniques are used to clone DNA sequences encod ing antigens of choice into eukaryotic expression plasmids, which are readily and economically amplified in bacteria and recovered with a hi gh degree of purity. For immunization, plasmid DNA is either coated on to microscopic gold particles and bombarded into skin using a gene gun or injected into skin or muscle. Expression of administered genes res ults in the induction of humoral and cellular immune responses against the encoded antigen. DNA immunization is capable of inducing protecti ve immunity in a number of animal models of infectious disease and can cer. Recent studies suggest that antigen-specific cytotoxic T lymphocy te induction occurs through the presentation of appropriate peptides i n the context of major histocompatibility complex molecules on bone ma rrow-derived professional antigen presenting cells. Following DNA inoc ulation into the skin, Langerhans cells and/or dermal dendritic cells are believed to acquire the newly synthesized antigen, either through direct transfection or via antigen uptake from transfected keratinocyt es, and migrate to regional lymph nodes where they stimulate primary T cell responses, The nature of the immune response depends on the rout e, method, and timing of DNA delivery and can also be influenced by co -delivery of plasmids encoding immunomodulating cytokines like IFN-alp ha, IL-2, or IL-12 and costimulatory molecules like B7-1. While many a spects of the biology of cutaneous DNA immunization remain unknown, th e skin appears to offer unique potential as a target for DNA-based imm unization.