In the early 1990s it was discovered that genetically engineered DNA can be delivered in vaccine form to elicit an immune response. Years of research using DNA vaccines generated a great deal of excitement in the potential capabilities of this technology as well as frustration due to the failure of the vaccines to demonstrate high levels of vaccine-specific immunity in humans (which resulted from vaccine plasmids not getting into enough cells). Since then, there has been great progress in the scientific understanding and clinical advancement of this platform that has brought DNA vaccines back on a productive path. Several factors have contributed to this progress, including a high level of cooperation between industry, regulatory authorities, the public, and academicians and technical improvements such as gene optimization strategies, improved RNA structural design, novel formulations and immune adjuvants, and more effective delivery approaches.
DNA vaccines are comprised of optimized gene sequences (antigenic or immune adjuvant genes) that are generated synthetically or by PCR. This optimized gene sequence is inserted into the multiple cloning region of a plasmid backbone, purified, and then delivered intradermally, subcutaneously, or intramuscularly by one of many possible delivery methods. Upon delivery and by using the host cellular machinery, the plasmid enters the nucleus of transfected local cells (myocites, keratinocytes, and resident antigen presenting cells (APCs)). This is where the generation of foreign antigens as proteins occurs. Outside of the cell, “these host-synthesized antigens can become the subject of immune surveillance in the context of both major histocompatibility complex (MHC) class I and class II molecules of APCs in the vaccinated host. Antigen loaded APCs then travel to the draining lymph nodes through the afferent lymphatic vessel. In the lymph nodes, the antigen loaded APCs present antigenic peptide MHC complexes in combination with signaling by co-stimulatory molecules to native T-cells. This interaction provides the essential secondary signals to stimulate an immune response and to activate T cells, B cells and antibody production cascades that will recognize the viral protein and attack any virus bearing it in the future. Together, both humoral and cellular immune responses are engendered, which can create a powerful defense against most infectious diseases.”
Unlike conventional vaccines that use live attenuated viruses, killed viral particles, or recombinant viral proteins, DNA vaccines are non-live, non-replicating and non-spreading vaccines that have little to no risk of reversion to a disease-causing form or secondary infection. As a result, DNA vaccines can be re-administered on a regular and repetitive basis without safety issues or vector interference concerns, are stable, easily stored, and can be quickly manufactured on a large scale.
There are numerous animal and human clinical trials underway to test DNA vaccines for preventive and therapeutic effects against multiple infectious diseases and cancers, some of which include HIV, influenza, hepatitis B and C, human papillomavirus, melanoma, lymphoma, and cervical, prostate, colon, and breast cancer. Many current and completed trials have used recombinant viral vector platforms, cytokine immune activators, or DNA vaccines in combination with other traditional vector-based vaccines as a prime-boost strategy to enhance the immune responses resulting from these vaccines.
Further advancement of DNA vaccines will continue to be an exciting adventure and will continue to require a highly productive and collaborative effort amongst the industry, regulatory authorities, academicians, and funding organizations.