A Conditionally Replicating Virus as a Novel Approach Toward an HIV Vaccine

This chapter examines a conditionally replicating virus as a novel approach toward an HIV vaccine. Live-attenuated virus vaccines have proven to be highly successful at inducing protective immunity against pathogenic viruses, such as smallpox, polio, and measles. The development of an HIV-1 variant by replacing the natural gene expression mechanism of the virus with an inducible regulatory system is presented. The Tet–rtTA system seems to be the ideal regulatory system to control replication of a conditional live HIV-1 virus vaccine. It is found that controlling virus replication through rtTA instead of tTA will avoid the long-lasting administration of Tc or dox that would be required with tTA. It is observed that to transform the constitutively replicating HIV-1 virus into a conditional live variant, the viral genome was mutated to inactivate the Tat–TAR transcription regulation mechanism and to integrate the Tet system. The 5´TAR RNA hairpin is formed by base pairing of nucleotides from positions +1to +57 relative to the start site of transcription. The substitution of the nef gene with the rtTA gene is also elabroated.