DNA Vaccines Bypass the Need to Purify Antigens

DNA VACCINES BYPASS THE NEED TO PURIFY ANTIGENS

The principle of the DNA vaccine is to just administer DNA that encodes appropriate antigens instead of providing whole microorganisms or even purified proteins. Naked DNA vaccines consist of plasmids carrying the gene for the antigen under control of a strong promoter. The intermediate early promoter from cytomegalovirus is often used because of its strong expression. The DNA is then injected directly into muscle tissue. The foreign genes are expressed for a few weeks and the encoded protein is made in amounts sufficient to trigger an immune response. The immune response is localized to the chosen muscle, which helps avoid side effects. In addition, purified DNA is much cheaper to prepare than purified protein and can be stored dry at room temperature, avoiding the need for refrigeration. The best method of delivering DNA is attaching it to a microparticle with a cationic surface (Fig. 6.27) because the surface binds to the negatively charged phosphate backbone. After the DNA-coated microparticle enters the cells, the DNA is slowly released from the bead and is then converted into protein. The slow release of DNA elicits a better immune response than a large direct dose of DNA. The immune system has to create more and more antibodies to the proteins.

One problem with DNA vaccines is that certain DNA sequences may induce an immune response directly. In particular, some DNA sequence motifs found in bacterial DNA may elicit strong immune responses, which in turn may cause the body to target its own DNA, thus generating an autoimmune response.