The Emerging Role of DNA Vaccines

W. Michael McDonnell, MD, Western Washington Medical Group, and Frederick K. Askari, MD, PhD, University of Michigan.

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In This Article

How DNA Vaccines Differ From Traditional Vaccines

DNA vaccines are able to stimulate cell-mediated immunity whereas traditional vaccines stimulate humoral immunity.[11] Traditional vaccines have been developed against numerous bacterial and viral pathogens, but the development of vaccines against many important viruses has been elusive. Generally where immunization has been successful, the host immune system makes neutralizing antibodies against the pathogen. In the case of HBV, antihepatitis B surface antigen antibody (HBsAb) is protective. Typically, individuals with detectable levels of HBsAb have been exposed to HBV, have overcome the infection and are no longer infected.

However, many antiviral antibodies are not capable of protecting against infection. The presence of antibody against most viruses is a marker of chronic ongoing infection -- not immunity. Failure of the antibody system to clear virus is common and it is generally held that cell-mediated immunity rather than humoral immunity has a dominant role in fighting viral infections. Viruses live and replicate inside cells, seizing the host's synthetic machinery, and therefore are sheltered from antibody surveillance. Cell-mediated immunity is needed to detect and destroy these infected cells. Antibodies play an essential role in neutralizing extracellular virus, especially at the time virus is released into the blood stream or extracellular space after an infected cell has been lysed either by the virus itself following replication or a cytotoxic T cell. Effective antibodies are often directed at viral surface antigens (envelope proteins) because these are the epitopes most available in intact virions.

However with chronic viral infections the virus is often able to evade the humoral system through a high rate of mutation of the envelope protein. In chronic infections such as HCV and HIV, many different mutations in the envelope epitopes are often found in a single infected individual. These are known as quazispecies. Influenza is not a chronic infection but has considerable genetic drift (mutations) in the envelope structure, which is an important factor in the failure of influenza subunit vaccines directed at the envelope glycoprotein to prevent reinfection from one year to the next.

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