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2001 OCT 17 - (NewsRx.com & NewsRx.net) -- by Michael Greer, senior medical writer - Live-attenuated HIV vaccines based on plasmid DNA or proviral constructs are not yet a promising area of study, researchers in Australia argue.
"Delivery of live-attenuated HIV-1 vaccines as plasmid DNA would overcome problems associated with production of attenuated HIV-1 strains," explained S.J. Kent and colleagues at the University of Melbourne and the Macfarlane Burnet Centre for Medical Research in Fairfield.
However, with current technology, these types of vaccines are too inefficient for effective use, Kent and team reported.
Although wild-type proviral HIV constructs replicated efficiently in human skin ex vivo, attenuated constructs with deletions in Nef, Vpr, or the long terminal repeat (LTR) displayed far weaker replicative abilities. Early Tat coexpression from another plasmid did not solve this problem, the researchers noted.
Plasmids driven by the LTR, necessary for gene expression from live-attenuated HIV vaccines, induced the expression of reporter genes after inoculation into ex vivo human skin or live macaques. However, the LTR was up to 20 times less efficient than the immediate-early cytomegalovirus promoter in this regard, study data showed.
An LTR with deletions in the U3 ...