DNA immunization as an efficient strategy for vaccination

Abstract

The field of vaccinology provides excellent promises to control different infectious and non-infectious diseases. Genetic immunization as a new tool in this area by using naked DNA has been shown to induce humoral as well as cellular immune responses with high efficiency. This demonstrates the enormous potential of this strategy for vaccination purposes. DNA vaccines have been widely used to develop vaccines against various pathogens as well as cancer, autoimmune diseases and allergy. However, despite their successful application in many pre-clinical disease models, their potency in human clinical trials has been insufficient to provide protective immunity. Several strategies have been applied to increase the potency of DNA vaccine. Among these strategies, the linkage of antigens to Heat Shock Proteins (HSPs) and the utilization of different delivery systems have been demonstrated as efficient approaches for increasing the potency of DNA vaccines. The uptake of DNA plasmids by cells upon injection is inefficient. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target Antigen-Presenting Cells (APCs) are effective in animal models. Alternatively, different regimens called prime-boost vaccination are also effective. In this regimen, naked DNA is utilized to prime the immune system and either recombinant viral vector or purified recombinant protein with proper adjuvant is used for boosting. In this review, we discuss recent advances in upgrading the efficiency of DNA vaccination in animal models.

Keywords: Adjuvant; DNA vaccination; Delivery system; Infectious disease; Prime-boost vaccination.

Figure 1

Molecular pathways of DNA vaccine by presenting the antigen to the T cells through the MHC class I and class II molecules. In endogenous pathway, the DNA plasmid enters the cell and nucleus, where the gene is transcribed into messenger RNA (mRNA). Then, mRNA is translated into protein by ribosomes in the rough endoplasmic reticulum (ER, not shown). In the cytosol the protein is cleaved by proteasomes, and the short peptides (contaning 8 to 10 amino acids) are transported into the ER with transport associated proteins (TAP1 and TAP2) and bind to MHC class I molecules. After binding, the complex is transported through the Golgi apparatus to the cell surface, where it can be recognized by cytotoxic T cells (CD8+) and stimulation of cell-mediated immunity occurs. In exogenous pathway, antigen-presenting cells take up extracellular proteins by either endocytosis or phagocytosis. MHC class II molecules in ER pass through the Golgi apparatus and enter acidified endosomes in which the foreign protein has been fragmented into peptides (Endolysosomal degradation pathway). The MHC–peptide complex is then brought to the cell surface, where it can be recognized by helper T cells (CD4+). Specific helper T cells recognize this antigen peptide/MHC class II molecule complex and are activated to produce help in the form of cytokines. These cytokines have many activities, depending on their types, helping B cell to produce antibody and helping cytolytic T lymphocyte (CTL) responses

Figure 2

Peptide-based nucleic acid delivery systems must be able to: 1) tightly condense DNA into small, compact particles; 2) target the condensate to specific cell surface receptors; 3) induce endosomal escape and 4) target the DNA cargo to the nucleus for target gene expression