Adjuvants for plasmid DNA vaccines

In the late 1980s, Jon Wolff of the University of Wisconsin and Phil Felgner here at Vical were screening cationic lipids for their ability to encapsulate and deliver purified plasmid DNA into mouse tissues. They discovered that direct injection of lipid-DNA complexes into muscle resulted in measurable protein expression. A belated control experiment without lipid led to the serendipitous discovery that "naked" plasmid DNA was taken up and expressed in muscle to a greater extent than DNA-lipid complexes (1). This key observation led to the demonstration that i.m. injection in mice of a standard 50 μg of plasmid DNA encoding a reporter gene becomes readily expressed exclusively in myofiber cells at 180 pg of gene product per muscle (2). More recently, plasmid DNA expression vectors were improved such that an average of 300 ng of gene product could be produced from single intramuscular (i.m.) injections of plasmid DNA, and up to 40 μg of gene product could be produced after multiple injections (3 and J. Hartikka, unpublished observations).