ABSTRACT
L ive viral vector vaccines derived by the insertion o f genes encoding sequences from disease organisms offer a number o f advantages over live attenuated vaccines, inactivated vaccines, subunit or D N A approaches. The evolution o f any successful vaccine must address issues such as safety, efficacy, host range, genetic stability, vector immunity, ease o f use, and manufacturing costs. One o f the most important safety features o f live viral vectors is that the recipients may be immunized against specific antigens from pathogenic organisms without exposure to the disease agent itself. Safety is further regulated by the selection o f a viral vector that is either attenuated for the host or unable to replicate in the host although still able to express the heterologous antigen o f interest. A vaccine strain that has a history o f safety in the target species offers an additional safety feature. However, the possibility o f systemic infection in immunocompromised individuals must be considered in the development o f all live viral vaccines. Several systems have been developed in which the vector is deleted o f essential genes and preparation o f the vaccine is carried out in cell systems that provide the missing function. With attenuated vectors, the possibility o f reversion to a more virulent strain may be a concern; the use o f a vector that has extensive engineered deletions can reduce the chance o f reversion by recombination with wild type viruses. Other safety issues with live viral vectors include integra tion into the host genome and the possibility that insertion o f a foreign gene may cause a change o f pathogenicity or host range.
