Gene-based Vaccines

Abstract

Gene-based vaccines, like other areas of gene therapy, encompass technologies ranging from plasmid DNA to viral vectors. Many efforts focused upon the use of plasmids, because of a desire to have delivery systems which were themselves non-immunogenic and could hence be readministered. The intrinsic efficiency of viruses and bacteria to infect cells has led to efforts to utilize them as vaccine vectors. Because the early generations of DNA vaccines are fairly inefficient in terms of DNA transduction and resultant immunogenicity, a variety of means to increase their potency will be discussed. Specifically, in addition to addressing the various mechanisms whereby transduction can be increased, the delivery of DNA by in vivo electroporation and microparticle formulation will be descried. Alpha-virus-based systems, both plasmid and viral particle will also be described. The alpha virus systems have a number of potential mechanisms whereby they may have increased potency compared to conventional plasmid vaccines including the production of multiple copies of mRNA directed by the viral nonstructural proteins (NSP) the induction of increased gamma interferon and MHC Class 1 expression, and the NSP-induced apoptosis of transduced cells. A further development has been the selection of alpha viral particles that have tropism for Dendritic cells. In an effort to have antigen expressed directly in professional antigen presenting cells. Evidence of the use of mixed-modality vaccines to increase immune responses will also be presented. These delivery systems will be described in the context of vaccine applications, but may also have therapeutic applications, not only for immunotherapy but for the provision of therapeutic proteins.