Genetically Modified Viruses  Vaccines by Design

John   R.   Stephenson

Abstract

Vaccination has been one of the most successful and cost-effective healthinterventions ever employed. One disease (smallpox) has been eradicated, another(poliomyelitis) should disappear early in the new millennium and a third (measles)should follow shortly after. Conventional vaccines usually depend on one of threedevelopment processes, attenuation of virulent organisms (by passage in cell cultureand(slash)or experimental animals), killing of virulent organisms (by chemical inactivation) or the purification of immunogenic molecules (either proteins or carbohydrates) from wholeorganisms. These traditional processes, although serendipitous and poorly understood, have produced effectivepharmaceutical products which give excellent protection against diseases such as smallpox, rabies, measles,yellow fever, tetanus and diphtheria. In spite of these successes however, the application of these protocolshave failed to produce safe and efficacious vaccines against other infectious diseases which kill or maim tens ofmillions of people every year. The most important of these are malaria, AIDS, herpes, dengue fever and someforms of viral hepatitis. Consequently, fundamentally new technologies are required to tackle these important infections. One of themost promising has been the development of genetically modified viruses. This process normally involvestaking a proven safe and efficacious vaccine virus, such as vaccinia or adenovirus, and modifying its genometo include genes coding for immunogenic proteins from other viruses such as HIV or measles. This reviewwill describe the generation of such novel vaccine vectors and compare their advantages and shortcomings. In addition the literature describing their use as experimental vaccines will also be reviewed.

Keywords: Genetically Modified Viruses, Vaccines, Vaccination, Rabies, Poliomyelitis, Measles, Yellow fever, Tetanus, Diphtheria, Smallpox