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Vaccines Through Biotechnology
Understanding the Immune System

Adapted by Mary Shomon

Through genetic engineering, scientists can isolate specific genes and insert them into DNA of certain microbes or mammalian cells; the microbes or cells become living factories, mass producing the desired antigen. Then, using another product of biotechnology, a monoclonal antibody that recognizes the antigen, the scientists can separate the antigen from all the other material produced by the microbe or cell. This technique has been used to produce immunogenic but safe segments of the hepatitis B virus and the malaria parasite.

In another approach, scientists have inserted genes for desired antigens into the DNA of the vaccinia virus, the large cowpox virus familiar for its role in smallpox immunization. When the reengineered vaccinia virus is inoculated, it stimulates an immune reaction to both the vaccinia and the products of its passenger genes. These have included, in animal experiments, genes from the viruses that cause hepatitis B, influenza, rabies, and AIDS.

Instead of adding a gene, some scientists have snipped a key gene out of an infectious organism. Thus crippled, the microbe can produce immunity but not disease. This technique has been tried with a bacterium that causes the severe diarrheal disease cholera; such a vaccine is commercially available against a virus disease of pigs.

A totally different approach to vaccine development lies in chemical synthesis. Once scientists have isolated the gene that encodes an antigen, they are able to determine the precise sequence of amino acids that make up the antigen. They then pinpoint small key areas on the large protein molecule, and assemble it chemical by chemical. Wholly synthetic vaccines are being explored for malaria and for the major diarrheal diseases that are so devastating in developing countries.

Another pioneering vaccine strategy exploits antiidiotype antibodies (see A Web of Idiotypes). The original antibody (or idiotype) provokes an antiantibody (or antiidiotype) that resembles the original antigen on the disease-causing organism. The antiidiotype will not itself cause disease, but it can serve as a mock antigen, inducing the formation of antibodies that recognize and block the original antigen. To make such a vaccine, scientists inject animals with a monoclonal antibody (idiotype) against a disease-causing microorganism, then harvest the antiidiotypes produced in response.

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