Figure 18
Strategy for constructing a subunit vaccine for herpes simplex.
Piggyback Vaccines
Another area of potential significance involves the use of genetic engineering to produce subunit vaccines against viruses such as those that cause herpes and hepatitis. Genes encoding part of the protein-polysaccharide coat of the herpes simplex virus or hepatitis B virus are spliced into a fragment of the vaccinia (cowpox) virus genome (figure 18). The vaccinia virus, which British physician Edward Jenner used almost 200 years ago in his pioneering vaccinations against smallpox, is now used as a vector to carry the herpes or hepatitis viral coat gene into cultured mammalian cells. These cells produce many copies of the recombinant virus, which has the outside coat of a herpes or hepatitis virus. When this recombinant virus is injected into a mouse or rabbit, the immune system of the infected animal produces antibodies directed against the coat of the recombinant virus. It therefore develops an immunity to herpes or hepatitis virus. Vaccines produced in this way are harmless because the vaccinia virus is benign and only a small fragment of the DNA from the disease-causing virus is introduced via the recombinant virus. The great attraction of this approach is that it does not depend upon the nature of the viral disease. In the future, similar recombinant viruses may be injected into humans to confer resistance to a wide variety of viral diseases.
In 1995, the first clinical trials began of a novel new kind of DNA vaccine, one that depends not on antibodies but rather on the second arm of the body’s immune defense, the so-called cellular immune response, in which blood cells known as killer T cells attack infected cells. The infected cells are attacked and destroyed when they stick fragments of foreign proteins onto their outer surfaces that the T cells detect (the discovery by Peter Doherty and Rolf Zinkernagel that infected cells do so led to their receiving the Nobel Prize in medicine in 1996). The first DNA vaccines spliced an influenza virus gene encoding an internal nucleoprotein into a plasmid, which was then injected into mice. The mice developed strong cellular immune responses to influenza. New and controversial, the approach offers great promise.
Genetic engineering has produced commercially valuable proteins, gene therapies, and, possibly, new and powerful vaccines.
