Conventional immunization approaches utilize live attenuated pathogens, inactivated organisms, recombinant proteins or
polysaccharide antigens to induce protective immunity. Twenty years ago in a major breakthrough it was shown that immune
responses could instead be elicited by injecting plasmid DNA encoding relevant vaccine antigens [1-3]. This heralded the start
of DNA vaccination. DNA vaccines offer many potential advantages; including speed and simplicity of manufacture. Despite
early hype, this technology has yet to yield approved human products although there are already a number of approved
veterinary DNA vaccines suggesting human applications are only a matter of time . It should be remembered that
monoclonal antibodies took over 2 decades from initial discovery to final successful human application. By these standards
DNA vaccine technology is still in its relatively infancy.
Hence this special edition on DNA vaccines is timely to examine the state of the art in DNA vaccine technology. It is hoped
this collections of papers will help address the perennial question asked on all long journeys, “are we there yet?” These papers
convey a sense of the tremendous distance that DNA vaccine technology has come over the 20 years since its initial discovery.
In particular, issues of DNA vaccine safety have by and large been satisfactorily addressed, leaving vaccine efficacy as the only
real remaining challenge .
Despite the passage of time there is still a sense of excitement that surrounds the DNA vaccine field. These papers convey a
willingness of those in the field to press on to solve the remaining challenges to bring DNA vaccines to the human market. This
augurs well for the eventual success of DNA vaccine technology. A variety of key topics are covered by this collection. The
excellent review by Jim Williams describes the state of the art in DNA plasmid design. It highlights just how far plasmid
design has been advanced and explores how plasmids can be fine tuned for maximal protein expression. Kwilas et al., describe
a novel delivery approach that uses a jet injector device to deliver the plasmid intramuscularly without the need for a needle.
Interestingly this form of administration appears to also enhance plasmid expression and vaccine immunogenicity. Another area
where there have been major advances is the area of DNA vaccine adjuvants. Capitani et al. demonstrate that plasmids
encoding aggregation-promoting domains act as DNA vaccine adjuvants by triggering frustrated autophagy leading to caspase
activation and apoptotic cell death. The induction of cell death is common to traditional vaccine adjuvants including alum and
squalene oil emulsions , but poses safety risks as excess cell death may trigger unwanted side effects and even autoimmunity
in susceptible individuals [7, 8]. No discussion of DNA vaccines would be complete without including electroporation as a
method of enhancing plasmid expression. Davtyan et al. describe studies on electroporation settings to maximize delivery of an
Alzheimer’s disease DNA vaccine encoding a β-amyloid epitope. Electroporation remains a potent tool for maximizing DNA
delivery but with the downsides of inconvenience, cost and discomfort. Finally, Lucyna Cova examines the history of hepatitis
B DNA vaccine development, describing the many challenges encountered along the way. This is a story that could easily be
repeated for the many other DNA vaccines under development.
I trust this collection of papers on current DNA vaccine research will convince the reader that the field of DNA vaccines is
not dead, and in fact under the surface vigorous research and development efforts continue towards a key milestone which will
be approval of the first human DNA vaccine. Considering the more than 20 years that monoclonal antibody technology had to
spend in the wilderness before all their problems were solved and they became the pharmaceutical industry’s biggest success
story, DNA vaccines may yet have their time in the sun.