Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

Abstract

Advantages of DNA vaccination against infectious diseases over more classical immunization methods include the possibilities for rapid manufacture, fast adaptation to newly emerging pathogens and high stability at ambient temperatures. In addition, upon DNA immunization the antigen is produced by the cells of the vaccinated individual, which leads to activation of both cellular and humoral immune responses due to antigen presentation via MHC I and MHC II molecules. However, so far DNA vaccines have shown most efficient immunogenicity mainly in small rodent models, whereas in larger animals including humans there is still the need to improve effectiveness. This is mostly due to inefficient delivery of the DNA plasmid into cells and nuclei. Here, we discuss technologies used to overcome this problem, including physical means such as in vivo electroporation and co-administration of adjuvants. Several of these methods have already entered clinical testing in humans.

The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

“…DNA vaccines are made up of eukaryotic expression plasmids that carry an antigen of interest. When the DNA vaccine is injected into the body of an organism, the foreign target antigen is expressed in vivo, and this expression activates the body's immune system by inducing specific humoral and cellular immune responses [3,4]. In recent years, rapid progress has been made in the development of DNA vaccines, particularly those that are used for the treatment of cancer and chronic infectious diseases [5].…”

Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

“…However, the first DNA-based vaccines showed suboptimal potency in large animal models and humans. Recently, enhanced delivery technologies, such as electroporation (37,38), and improved immunogenicity by triggering innate immune cells have increased the efficacy of DNA vaccines in clinical trials (39). Vaccines based on mRNA or RNA replicons are immunogenic in a variety of animal models, including nonhuman primates (40)(41)(42)(43)(44).…”

Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines

“…Because many conventional adjuvants work immediately after injection, their effect might be lower at the time the antigen is present. 33 In contrast, the use of plasmid encoding immunomodulatory proteins permits the coordinated delivery of antigens and adjuvants, tailoring the immune response to the demands of each particular disease. 7 Until now, most of the genetic adjuvants used in trials encode proteins that activate innate immune responses directly, such as cytokines, chemokines, signaling or costimulatory molecules.…”