DNA vaccines: an historical perspective and view to the future

Abstract

This review provides a detailed look at the attributes and immunologic mechanisms of plasmid DNA vaccines and their utility as laboratory tools as well as potential human vaccines. The immunogenicity and efficacy of DNA vaccines in a variety of preclinical models is used to illustrate how they differ from traditional vaccines in novel ways due to the in situ antigen production and the ease with which they are constructed. The ability to make new DNA vaccines without needing to handle a virulent pathogen or to adapt the pathogen for manufacturing purposes demonstrates the potential value of this vaccine technology for use against emerging and epidemic pathogens. Similarly, personalized anti-tumor DNA vaccines can also readily be made from a biopsy. Because DNA vaccines bias the T-helper (Th) cell response to a Th1 phenotype, DNA vaccines are also under development for vaccines against allergy and autoimmune diseases. The licensure of four animal health products, including two prophylactic vaccines against infectious diseases, one immunotherapy for cancer, and one gene therapy delivery of a hormone for a food animal, provides evidence of the efficacy of DNA vaccines in multiple species including horses and pigs. The size of these target animals provides evidence that the somewhat disappointing immunogenicity of DNA vaccines in a number of human clinical trials is not due simply to the larger mass of humans compared with most laboratory animals. The insights gained from the mechanisms of protection in the animal vaccines, the advances in the delivery and expression technologies for increasing the potency of DNA vaccines, and encouragingly potent human immune responses in certain clinical trials, provide insights for future efforts to develop DNA vaccines into a broadly useful vaccine and immunotherapy platform with applications for human and animal health.

Evaluation of Drug Toxicity for DNA Vaccine Candidates Against Infectious Diseases: Hepatitis C as Experimental Model

“…Several strategies, based on improvement on formulation or delivery vehicles have been or are currently being evaluated as alternative for reducing DNA dose levels or in order to increase immunogenicity of DNA vaccine candidates (Liu, 2011). However, although some of these strategies have succeeded at increasing the ability of DNA to reach the intracellular space as well as enhance immunogenicity, the risk for greater possibility of an undesired integration event is also bigger.…”

“…Such studies are designed to identify both, intrinsic toxicity of the vaccine candidate, as well as immunotoxicity arising from the host immune response after its administration. Accumulated data uniformly suggest that DNA vaccines are safe (reviewed by Liu, 2011). Mice and rats have been usually used as "first" species to study the toxicity of DNA vaccines.…”

“…Compared with many conventional vaccines, DNA vaccines are relatively stable. Moreover, DNA vaccines are rapid to construct and their manufacture is generic (Liu, 2011). The above mentioned advantages have resulted attractive for the application of DNA vaccination in the infectious disease field in humans.…”

Is electroporation decisive for the efficacy of DNA vaccine against house dust mite allergy?

“…Whether these antiallergy effects can be induced in humans still remain to be fully demonstrated. But the failure to translate the promising results from preclinical evaluation of anti-infectious/cancer diseases DNA vaccines to clinical trials clearly highlighted that DNA-based vaccines are basically weak immunogens in humans [6,7]. The poor DNA vaccine immunogenicity results more likely from a combination of factors including the limitation of the DNA doses in humans as well as ineffective cellular DNA uptake when administered by conventional injection.…”

“…By their ability to elicit mainly antigen-specific cytolytic T-lymphocyte (CTL), Th1-biased humoral and cellular immune responses (IgG/IFNg), DNA vaccines could represent a promising approach in the development of safer and more effective anti-allergy immunotherapies [6]. Indeed, numerous studies evidenced the prophylactic as well as the therapeutic effects of vaccinations with allergen encoding DNA plasmids to prevent and to revert respectively the allergic response in small rodents through the induction of allergen-specific Th1 immunity as well as tolerance mediated by Treg cells [7].…”