DNA vaccination

DNA vaccination is a technique for protecting against disease by injection with genetically engineered DNA so cells directly produce an antigen, producing a protective immunological response. DNA vaccines have potential advantages over conventional vaccines, including the ability to induce a wider range of immune response types. DNA vaccination is a technique for protecting against disease by injection with genetically engineered DNA so cells directly produce an antigen, producing a protective immunological response. DNA vaccines have potential advantages over conventional vaccines, including the ability to induce a wider range of immune response types. Several DNA vaccines are available for veterinary use. Currently no DNA vaccines have been approved for human use. Research is investigating the approach for viral, bacterial and parasitic diseases in humans, as well as for several cancers. Vaccines have eliminated naturally occurring smallpox, and nearly eliminated polio, while other diseases, such as typhus, rotavirus, hepatitis A and B and others are well controlled. Conventional vaccines cover a small number of diseases, but are not effective at controlling many other infections. First generation vaccines are whole-organism vaccines – either live and weakened, or killed forms. Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce killer T-cell (TC or CTL) responses, helper T-cell (TH) responses and antibody immunity. However, attenuated forms of a pathogen can convert to a dangerous form and may cause disease in immunocompromised vaccine recipients (such as those with AIDS). While killed vaccines do not have this risk, they cannot generate specific killer T cell responses and may not work at all for some diseases. Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific protein antigens (such as tetanus or diphtheria toxoid) or recombinant protein components (such as the hepatitis B surface antigen). They can generate TH and antibody responses, but not killer T cell responses. DNA vaccines are third generation vaccines. They contain DNA that codes for specific proteins (antigens) from a pathogen. The DNA is injected into the body and taken up by cells, whose normal metabolic processes synthesize proteins based on the genetic code in the plasmid that they have taken up. Because these proteins contain regions of amino acid sequences that are characteristic of bacteria or viruses, they are recognized as foreign and when they are processed by the host cells and displayed on their surface, the immune system is alerted, which then triggers immune responses. Alternatively, the DNA may be encapsulated in protein to facilitate cell entry. If this capsid protein is included in the DNA, the resulting vaccine can combine the potency of a live vaccine without reversion risks. In 1983, Enzo Paoletti and Dennis Panicali at the New York Department of Health devised a strategy to produce recombinant DNA vaccines by using genetic engineering to transform ordinary smallpox vaccine into vaccines that may be able to prevent other diseases. They altered the DNA of cowpox virus by inserting a gene from other viruses (namely Herpes simplex virus, hepatitis B and influenza). In 2016 a DNA vaccine for the Zika virus began testing at the National Institutes of Health. The study was planned to involve up to 120 subjects between 18 and 35. Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. The NIH vaccine is injected into the upper arm under high pressure. Manufacturing the vaccines in volume remains unsolved. Clinical trials for DNA vaccines to prevent HIV are underway.