Chapter 2.4 - DNA vaccination: A role for liposomes

Abstract

This chapter discusses DNA vaccination. DNA immunization is one of the exciting spin offs of gene therapy. It arose from the unexpected observation that injected purified plasmid DNA containing encoding sequences for a protein immunogen and regulatory elements necessary for their expression, transfects cells whereupon the protein produced induces humoral and cell-mediated immunity. A major advantage of DNA-based immunization over conventional sub-unit vaccines is that it mimics, at least to some extent, immune responses seen on viral infections. Several pathways leading to Thl and Th2 immunity following DNA vaccination include secretion of the antigen by the transfected muscle cells and its subsequent processing and eventual presentation by resident Langerhans or infiltrating antigen presenting cell (APC); release of antigen from transfected muscle cells following their death via a cytotoxic T cell response; and, possibly, transfection of both muscle cells and resident APC leading to a simultaneous activation of the T cell subsets. A variety of plasmid DNAs can be quantitatively incorporated by the dehydration–rehydration method into multi-lamellar liposomes composed of PC and DOPE alone or supplemented with anionic or cationic lipids. Immunization with liposomal DNA is not major histocompatibility complex (MHC) restricted and can have important implications in human and veterinary immunization programs.