Classical Live Viral Vaccines

Abstract

Classical, live viral vaccines have been developed by adapting viruses by serial passages in animals, tissue or cell cultures during which multiple mutations in the viral genome have accumulated. The majority of vaccines in use today were developed in this way and a number of similar investigational vaccines are currently in development. The principal advantage of live vaccines is that they mimic natural infection and induce durable immunity, including cytotoxic T cell responses that are not generated by soluble proteins and inactivated vaccines. Recent studies of gene activation following a live vaccine (yellow fever 17D) have shed light on the role of innate immune responses in provoking strong, polyfunctional adaptive immunity following the administration of live vaccines. The principal disadvantage of live vaccines is that, occasionally, infection caused by the live vaccine causes adverse events resembling the parental (virulent) virus. Such events can be due to reversions in critical attenuating mutations or to host-specific susceptibility factors. The attenuating mutations in live vaccines increase the inapparent: apparent infection ratio compared to the parental virus, but overt infection (adverse events) while far less frequent than in natural infection can still occur. This problem is inconsequential for infections that are typically mild or self-limited, such as measles, mumps, rubella, and varicella, but can be devastating for infections that are frequently lethal such as yellow fever or in individuals who are immunocompromised. Despite these issues, live vaccines have had dramatic benefits in reducing the incidence of the most important infections of humankind, and in one case (smallpox) a live vaccine helped eradicate a viral disease.