A Vaccine for All Seasons; Genetic Engineering Is Remodeling the Smallpox Vaccine to Provide Immunity against Many Other Diseases
Miller, Julie Ann, Science News
A Vaccine for All Seasons
Vaccinia virus is the champion of immunizations. It makes up the vaccine responsible for the worldwide eradication of smallpox, an unprecedented achievement in preventive medicine. But since its triumph over smallpox, vaccinia virus has not been permanently retired from combat. With recombinant DNA methods, scientists are attempting to retool the live viral vaccine to fortify people and animals against a variety of diseases, ranging from influenza to malaria.
"Clinical trials have not yet started, but animal tests seem highly encouraging,' said scientists in a summary report at the recent Dahlem Workshop on Biotechnology, held in West Berlin. "The potential . . . seems overwhelming.'
"Live recombinant vaccines are a blend of two arts,' said Enzo Paoletti of the New York State Health Department laboratories in Albany. The "old art' is the attenuation of natural disease-causing agents to create an organism that produces immunity without disease. The "new art' is the strategy now being used to develop many vaccines: the identification and laboratory production of specific components of a pathogen that can create immunity, even without the rest of the infectious agent. Some such "subunit' vaccines, including hepatitis B vaccine and the vaccine against childhood meningitis, have already reached the market. But subunit vaccines do not reproduce in the body, so they require large amounts of material that may be difficult and expensive to produce. In addition, the body generally will mount only a weak immune response to an isolated chemical.
The blended strategy behind the recombinant vaccinia approach is to choose an immunity-creating component of a disease organism, as in the subunit vaccine approach. But instead of making this component in isolation, scientists snap its gene into the DNA of the vaccinia virus. The foreign gene then can be inserted in a location that disrupts a natural gene of the vaccinia, thereby further attenuating it. When a person or animal is inoculated with the remodeled vaccinia, a local infection results. The virus, carrying the foreign gene, replicates in the host cell and induces an immune response both to the vaccinia virus and to the microorganism that contributed the foreign gene.
Vaccinia, a large and rather complex virus containing about 200 genes, has an impressive capacity for carrying excess baggage. Scientists have calculated that the virus could accept several dozen foreign genes and still successfully infect cells and replicate. Thus, a single vaccine potentially could immunize the recipient against more than a dozen diseases. Scientists envision vaccinia vaccine customized by inserting "cassettes' of genes to meet the immunization needs of people or livestock with particular susceptibilities in a particular geographic area.
Theoretically, many viruses could be used as carriers of immunity-provoking genes. (Indeed, there is one group of researchers working on inserting foreign genes into a herpes simplex virus.) But those scientists working on vaccinia argue that there is no need to look further. "Vaccinia has a history the others don't have,' says Paoletti.
Their enthusiasm rests on the almost two centuries of experience with vaccinia for smallpox prevention. "The vaccine was inexpensive to produce,' says Paoletti. "It could be stabilized as a freeze-dried preparation that could be shipped to all parts of the world in the absence of refrigeration. Administration of the vaccine did not require highly trained medical personnel nor sophisticated, expensive medical equipment.' A genetically engineered vaccinia vaccine would be expected to have the same advantages.
The vaccinia virus is also particularly well suited for laboratory research because it has a very wide range of hosts, so potential vaccines can be tested on most laboratory animals. In fact, new vaccinia vaccines are expected to be developed for veterinary practice before any come into clinical use in humans. …