DNA Vaccines May Get Around Antigen Shifting


Vaccination against diseases such as small pox, measles, and polio involves the introduction into your body of a dead or disabled pathogen or of a harmless microbe with pathogen proteins displayed on its surface. The vaccination triggers an immune response against the pathogen, and the bloodstream of the vaccinated person contains B cells which will remember and quickly destroy the pathogen in future infections. However, for some diseases, vaccination is nearly impossible because in a process called antigen shifting, the pathogens change over time and are no longer recognized by the B cells. Influenza, for example, changes its surface proteins yearly. The pathogen responsible for sleeping sickness, trypanosomes, changes its surface proteins every few weeks.

A new type of vaccine, based on DNA, may prove to be effective against almost any disease. The vaccine makes use of the killer T cells instead of the B cells of the immune system. Pathogens floating around in the blood stream are recognized by B cells of the immune system, which then signal the production of antibodies against the pathogen. Once inside a cell, however, pathogens are protected from antibodies. Only when the cell is able to display on its outside some of the surface proteins from the pathogen it contains will killer T cells come and destroy that cell. The problem is, the cell will not stick bits of the pathogen's proteins to its surface unless it contains a live version of the disease-agent. This means that any vaccine will have to be alive and may cause an actual infection.

DNA vaccines avoid this risk. They consist of a plasmid, a harmless circle of bacterial DNA, that contains a gene from the pathogen that encodes an internal protein, one which is critical to the function of the pathogen and does not change. When this plasmid is injected into cells, the gene they carry is transcribed into protein but is not incorporated into the DNA of the cell's nucleus. Fragments of the pathogen protein are then stuck on the cell's membrane, marking it for destruction. In actual infections later, the immune system will be able to respond immediately. Studies are now underway to isolate the critical, unchanging proteins of pathogens and to investigate fully the use of the vaccines in humans.

Source: "Spiralling to a new vaccine" The Economist, June 8, 1996.

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