| 摘要 |
The present invention relates to inducible viral replicons as regulatable live-attenuated vaccine candidates. In particular, it relates to the HIV-rtTA replicon whereby, aiming for regulated expression of the replicon, the rtTA gene has been inserted into the HIV1-Nef gene (i.e. under control of Nef regulatory elements), the TetO elements have been inserted into one or either LTRs, and the NF-Kappa-B sites of said LTRs have of have not been mutated. Aiming for further attenuation, the TAR hairpin and eventually also the Tat gene have been mutated. A conditional cytotoxic gene (e.g. HSV-tk) can eventually also be inserted into the replicon to provide for improved biosafety. Said replicon is intended to be used as live-attenuated HIV1 vaccine, but forced evolution (i.e. genetic drift of HIV due to the relatively poor fidelity of HIV1 RT) could be used to improve the present mutants, as well as to select for modified/improved rtTA-TetO regulatory systems. <IMAGE> |
