The role of particle-mediated DNA vaccines in biodefense preparedness.

Particle-mediated epidermal delivery (PMED) of DNA vaccines is based on the acceleration of DNA-coated gold directly into the cytoplasm and nuclei of living cells of the epidermis, facilitating DNA delivery and gene expression. Professional antigen-presenting cells and keratinocytes in the skin are both targeted, resulting in antigen presentation via direct transfection and cross-priming mechanisms. Only a small number of cells need to be transfected to elicit humoral, cellular and memory responses, requiring only a low DNA dose. In recent years, data have accumulated on the utility of PMED for delivery of DNA vaccines against a number of viral pathogens, including filoviruses, flaviviruses, poxviruses, togaviruses and bunyaviruses. PMED DNA immunization of rodents and nonhuman primates results in the generation of neutralizing antibody, cellular immunity, and protective efficacy against a broad range of viruses of public health concern.