A candidate live inactivatable attenuated vaccine for AIDS.
Open Access
- 3 September 1996
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 93 (18), 9810-9815
- https://doi.org/10.1073/pnas.93.18.9810
Abstract
The recent discovery of long term AIDS nonprogressors who harbor nef-attenuated HIV suggests that a naturally occurring live vaccine for AIDS may already exist. Animal models have shown that a live vaccine for AIDS, attenuated in nef, is the best candidate vaccine. There are considerable risks, real and perceived, with the use of live HIV vaccines. We have introduced a conditional lethal genetic element into HIV-1 and simian immunodeficiency virus (SIV) molecular clones deleted in nef. The antiviral strategy we employed targets both virus replication and the survival of the infected cell. The suicide gene, herpes simplex virus thymidine kinase (tk), was expressed and maintained in HIV over long periods of time. Herpes simplex virus tk confers sensitivity to the antiviral activity of acyclic nucleosides such as ganciclovir (GCV). HIV-tk and SIV-tk replication were sensitive to GCV at subtoxic concentrations, and virus-infected cells were eliminated from tumor cell lines as well as primary cell cultures. We found the HIV-tk virus to be remarkably stable even after being cultured in media containing a low concentration of GCV and then challenged with the higher dose and that while GCV resistant escape mutants did arise, a significant fraction of the virus remained sensitive to GCV.Keywords
This publication has 42 references indexed in Scilit:
- The nef Gene from a Long-Term HIV Type 1 NonprogressorAIDS Research and Human Retroviruses, 1996
- Genomic Structure of an Attenuated Quasi Species of HIV-1 from a Blood Transfusion Donor and RecipientsScience, 1995
- The enigma of HIV infectionCell, 1995
- Gene Therapy for Vascular Smooth Muscle Cell Proliferation After Arterial InjuryScience, 1994
- The relationship of IL-4- and IFNγ-producing T cells studied by lineage ablation of IL-4-producing cellsCell, 1993
- The selective ablation of interleukin 2-producing cells isolated from transgenic mice.The Journal of Experimental Medicine, 1993
- Fidelity of HIV-1 reverse transcriptase copying RNA in vitroBiochemistry, 1992
- Importance of the nef gene for maintenance of high virus loads and for development of AIDSCell, 1991
- ACYCLOVIR FOR SUSPECTED SYSTEMIC HERPES INFECTIONSThe Lancet, 1980
- Inhibition of herpes virus by a new compound—acyclic guanosineJournal of Antimicrobial Chemotherapy, 1979