Prospects for dna vaccination and viral diseases

Vaccine development has always been based on the induction of a potent and an anamnesic mmune response against an infectious agent. It is well known that the use of natural microorganisms for vaccine therapy is the more appropriate option; however, this approach does not always meet the fundamental characteristics of an ideal vaccine, especially in terms of secondary adverse effects. In the specific case of viral vaccines, the risks associated with the production of large quantities of infectious virus with low viral titres, the reversion to virulent forms due to the high frequency of viral RNA mutation and the high costs related to cell culture are some of the greatest challenges related to this strategy. DNA vaccines are novel tools capable of preventing infectious diseases; this kind of immunization represents a powerful opportunity to solving some of the above-mentioned problems, resulting very attractive option for the intracellular pathogens such as viruses. Current work with various models has provided knowledge in the understanding of nucleic acid immunization technology. The mechanism of action of a DNA vaccine consists in the delivery of the viral genetic material to the mammalian host cells using a plasmid which enters into cellular nucleus, making possible the transcription and translation of the foreign protein from the viral coding sequence contained on the plasmid. Once protein is expressed, this may be processed and presented by directly transfected cells or by cross-primed cells. DNA vaccines of non-replicating plasmid coding for the viral proteins provides a platform for the immune system to process and present viral epitopes in a manner analogous to natural infection. As a consequence, DNA vaccination has the ability to stimulate both effectors' arms of the specific protective immune response; cellular and humoral responses against the encoded gene products. DNA vaccination also offers the chance to manipulate the immune response induced by the vaccine, through the simultaneous administration of plasmids containing sequences encoding adjuvants, cytokines or other immunomodulatory molecules. Additionally these plasmids possess intrinsic adjuvant properties due to the presence of immunostimulatory sequences in the backbone of bacterial sequences composed of unmethylatedCpGdinucleotides, which represents one form of pathogen-associated molecule patterns (PAMP) capable of activating the innate immunity as well. Despite the success of intramuscularly injected non-replicating plasmid DNA coding for viral proteins able to elicit protective immune responses in laboratory animals, clinical trials have not successfully progressed. However, more research regarding dosage, appropriate antigens and potential applications needs to be conducted to improve the efficacy of these vaccines in humans. This review addresses the current state of progress and recent literature observations regarding potential approaches to DNA vaccination in the treatment of viral diseases.