AIDSWEEKLY Plus, Monday, 27 Mary 1997.
Daniel J. DeNoon, Senior Editor
A live HIV vaccine prototype not only protects against challenge after oral dosing but also reduces AIDS symptoms in animals already infected with SIV.
The most effective AIDS vaccine prototype yet tested is a live simian immunodeficiency virus (SIV) from which the nef gene has been deleted. But safety concerns about using a live retrovirus in humans have been heightened by reports that the vaccine is pathogenic when large doses are given orally to neonatal animals.
Last year, Tilahun D. Yilma of the University of California, Davis, reported that the vaccine is made vastly safer by replacing the missing nef gene with a gene encoding gamma interferon (IFN-g, see AIDS Weekly Plus, March 18, 1996). Even very high oral doses of the vaccine, dubbed SIV[HyIFN], was safe in neonatal animals.
This year, Yilma reported even more encouraging results.
"SIV[HyIFN] is non-pathogenic in neonates, who then develop immunity to challenge," Yilma said in a presentation to the 9th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held May 4-7, 1997, in Bethesda, Maryland.
Moreover, the vaccine apparently had a therapeutic effect in animals already infected with virulent SIV. It reduced SIV levels in animals persistently infected with the virus, and reduced viral load when administered soon after SIV challenge infection.
In their experiments, Yilma and colleagues orally administered 2x10(5) tissue culture infectious doses (TCID) of SIV[HyIFN] to three neonatal macaques. One week later, two of the three animals had detectable SIV[HyIFN] in peripheral blood mononuclear cells (PBMC) only. The third animal had detectable SIV[HyIFN] in both plasma and PBMCs up to three weeks after vaccination; it was the only monkey that developed high anti-SIV antibody titers.
Nine months after oral inoculation, all three animals and three control animals were challenged intravenously with virulent SIV[mac251]. Only the animal that demonstrated persistent SIV[HyIFN] infection resisted challenge; it remained immunologically normal 39 weeks after challenge.
"SIV[HyIFN] is non-pathogenic for newborn macaques and low-level infection with this novel vaccine is necessary for protection from infection with SIV[mac251]," Yilma concluded.
Of interest is the observation that gamma interferon production by cells infected with SIV[HyIFN] eventually ceases. The interferon expression cassette is deleted from the vaccine virus after six passages in culture, or about six weeks after in vivo inoculation.
"We are really not concerned about this," Yilma said last year. "It is fortunate that gamma interferon production only lasted the first four weeks after inoculation." - by Daniel J. DeNoon, Senior Editor
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