AIDSWEEKLY Plus, 18 March 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

Addition of a gene encoding gamma interferon makes a live prototype HIV vaccine both safer and more effective.

The vaccine, SIV[mac239] delta 3, under development by Therion Biologics Corp., is a live simian immunodeficiency virus (SIV) that has been genetically altered so that it is missing three vital genes: vpr, nef, and the gene encoding the Nef-responsive element (NRE).

But it takes SIV[mac239] delta 3 79 weeks to confer protection against infection with wild type virus. And there have been serious concerns about the safety of SIV[mac239] delta 3 in neonates (see the accompanying article in this issue).

Now researcher Tilahun D. Yilma of the University of California, Davis, reports that addition of a gene cassette encoding gamma interferon greatly improves SIV[mac239] delta 3. The new vaccine is dubbed SIV[HyIFN]

Yilma announced the findings at the Eighth Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS, held February 11-15, 1996, in Bethesda, Maryland.

"Lymphokines have the ability to attenuate a virus by a million-fold," Yilma said. "SIV[HyIFN] produces extremely reduced viral load."

Macaques injected with SIV[HyIFN] had far lower viral titers in their plasma and lymph nodes than did macaques injected with SIV[mac239] delta 3. Observations at the time of Yilma's report had been extended to 48 weeks.

Six monkeys inoculated with SIV[HyIFN] were far more resistant to challenge with 100 50% AIDS-infectious doses of wild-type SIV[mac251] than four animals that received SIV[mac239] delta 3. Two additional unvaccinated control animals died six and 18 weeks after challenge with the wild- type virus.

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. "It is fortunate that gamma interferon production only lasted the first four weeks after inoculation."

In experiments with neonate macaques, SIV[HyIFN] did not cause lethal infections - even at high doses.

"SIV[HyIFN] was shown to be non-pathogenic to neonates inoculated orally with 1x10(5) TCID[50] of SIV[HyIFN] twice in a 24-hour period," Yilma reported. "SIV[HyIFN] induced a transient, low-titer viremia in [four] newborn macaques that was cleared in less than six weeks."

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.