Replicating and non-replicating viral vectors for vaccine development

Abstract

IntroductionHistorically, live attenuated, replicating vaccines, rather than inactivated preparations, have provided the most effective protection against viral infection and disease. A partial list of such vaccines includes measles, mumps, rubella, polio, vaccinia, and yellow fever [1]. Notably, these vaccines elicit essentially life-long protective immunity. In contrast, immunity induced by inactivated or subunit vaccines is generally of more limited duration. A key factor in pursuit of the latter approaches is safety. Concerns arise not only over the possibility of disease induction in vaccinated individuals, particularly those who are immune compromised, but also over spread of the vaccine virus in the population. These issues are perhaps most evident in the efforts to develop a vaccine against HIV, where the target populations are likely to include some individuals already infected with HIV and perhaps immune suppressed as a result of their infection. Yet, nowhere is the urgency of vaccine development greater than in the AIDS field. In this chapter replicating and non-replicating viral vectors will be discussed with the focus largely on AIDS vaccine research, where a spectrum of both types of vector, each with its own unique advantages and disadvantages, is under development. Review of several in each category will illustrate issues faced in vector selection.Viral vectors for which both replicating and non-replicating forms are available include adenoviruses and poxviruses. Vectors designed primarily as replication-defective include adeno-associated virus, alphavirus, and herpesvirus, while replicating vectors include measles virus and vesicular stomatitis virus. Other vectors based on very successful vaccines have been less heavily exploited and will not be covered here. For example, poliovirus and yellow fever virus vaccines, both replication-competent, elicit life-long, persistent immunity. Yet as vectors, both exhibit not only genetic instability but also small insert capacity [2], limiting interest for vaccine development. Features of various viral vectors and recent results following their use will first be reviewed followed by a consideration of issues faced in vector selection. Table 1 lists some of the properties of each of the vectors covered here. Replicating and Non-replicating Adenovirus VectorsAdenoviruses (Ad) are among the most heavily exploited vectors for vaccine development. The virology and molecular biology of the double-stranded DNA virus were heavily investigated for years as part of gene therapy applications, providing an invaluable knowledge base for further development in the vaccine arena. Several Ad features are particularly attractive for vaccine use, including infection of both dividing and non-dividing cells, high levels of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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