Alphavirus vectors: Applications for DNA vaccine production and gene expression

Replication-deficient alphavirus vectors have been developed for efficient high-level transgene expression. The broad host range of alphaviruses has a llowed infection of a wide variety of mammalian cell lines and primary cult ures. Particularly, G protein-coupled receptors have been expressed at high levels and subjected to binding and functional studies. Expression in susp ension cultures has greatly facilitated production of large quantities of r ecombinant proteins for structural studies. Injection of recombinant alphav irus vectors into rodent brain resulted in local reporter gene expression. Highly neuron-specific expression was obtained in hippocampal slice culture s in vivo. Additionally, preliminary studies in animal models suggest that alphavirus vectors can be attractive candidates for gene therapy applicatio ns. Traditionally alphavirus vectors, either attenuated strains or replicat ion-deficient particles, have been used to elicit efficient immune response s in animals. Recently, the application of alphaviruses has been extended t o naked nucleic acids. Injection of DNA as well as RNA vectors has demonstr ated efficient antigen production. In many cases, protection against lethal challenges has been obtained after immunization with alphavirus particles or nucleic acid vectors. Alphavirus vectors can therefore be considered as potentially promising vectors for vaccine production. Copyright (C) 2001 S. Karger AG, Basel.