| abstract |
The present invention relates to inducible viral replicons asnregulatable live-attenuated vaccine candidates. In particular, itnrelates to the HIV-rtTA replicon whereby, aiming for regulatednexpression of the replicon, the rtTA gene has been inserted into thenHIV1-Nef gene (i.e. under control of Nef regulatory elements), the TetOnelements have been inserted into one or either LTRs, and the NF-Kappa-Bnsites of said LTRs have of have not been mutated. Aiming for furthernattenuation, the TAR hairpin and eventually also the Tat gene have beennmutated. A conditional cytotoxic gene (e.g. HSV-tk) can eventually alsonbe inserted into the replicon to provide for improved biosafety. Saidnreplicon is intended to be used as live-attenuated HIV1 vaccine, butnforced evolution (i.e. genetic drift of HIV due to the relatively poornfidelity of HIV1 RT) could be used to improve the present mutants, asnwell as to select for modified/improved rtTA-TetO regulatory systems. |