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Attenuated, doxycycline-inducible human immunodeficiency virus proviral molecular clones
Attenuated, doxycycline-inducible human immunodeficiency virus proviral molecular clones
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机译:强力霉素诱导的减毒人免疫缺陷病毒原病毒分子克隆
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摘要
The present invention provides an attenuated HIV vaccine comprising an HIV virus modified to replicate only in the presence of at least one tetracycline analogue. Additionally, the present invention provides a method for immunization of humans against HIV which comprises administering to a human a vaccine including an HIV virus modified to replicate only in the presence of at least one tetracycline analogue. Simultaneously, at least one tetracycline analogue is administered for a period of time to allow replication of the modified HIV virus in vivo sufficient to produce immunity. Preferably, the tetracycline analogue is doxycycline. A replication competent HIV-DoxT virus genome which can be controlled by the presence or. absence of doxycycline is produced by preparing a promoter, TetopTCAT; producing a provirus, pHIV-DoxT, using the TetopCAT promoter, and transfecting the pHIV-DoxT in cell lines in the presence of doxycycline. A replication competent HIV-DoxSp virus genome which can be controlled by the presence or absence of doxycycline is produced by preparing a promoter, TetopSpCAT; producing a provirus, pHIV-DoxSp, using the TetopCAT promoter, and transfecting the pHIV-DoxSp in cell lines in the presence of doxycycline. Anti-HIV vaccines are prepared using the HIV-DoxT and HIV-DoxSp virus genomes. These viruses and doxycycline are administered to human hosts. The doxycycline is administered for a time sufficient to build up immunity and then the administration of the drug is stopped so that the doxycycline-dependent viruses will no longer replicate.
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