Business Wire - Monday, February 1, 1999
Because the virus used in the study, the simian immunodeficiency virus (SIV), is a close relative of the human AIDS virus HIV-1, human vaccines built from weakened forms of HIV-1 are also likely to cause AIDS, the researchers say.
"Our study indicates that it is not safe to conduct human tests of AIDS vaccines made from live, weakened viruses," says Dana-Farber Cancer Institute's Ruth Ruprecht, M.D., Ph.D., who led the project. "There is a real risk of contracting AIDS from the vaccine itself."
The study, which is being published in the February issue of Nature Medicine, involves a group of rhesus monkeys that had been vaccinated with a live form of SIV which had been weakened, or attenuated, by the deletion of two genes and a regulatory segment involved in viral replication. The deleted genes are known as nef and vpr.
Of eight newborn monkeys that were given the vaccine orally or intravenously, six developed AIDS, and the other two showed early signs of immune disease. Long-term follow-up of 16 vaccinated adult monkeys found that four had a resurgence of virus in their blood; one of these developed early signs of immune disease and one died of AIDS.
The vaccine was based on the theory that a live, attenuated virus would stimulate immune protection against infection with intact SIV, but that the vaccine virus would be too weak to cause AIDS.
The theory seems to have been undone by SIV's (and HIV's) ability to mutate rapidly into new forms, Ruprecht says. Ruprecht and her colleagues found that in the monkeys that developed AIDS, the vaccine virus had evolved into different, shorter forms.
"The virus seems to be able to readapt and find a form that is better suited for replication after the genetic deletions have been made," Ruprecht says.
She points to two recent reports that underscore the dangers of AIDS vaccines made from nef-deleted HIV-1. One was contained in a letter published in the Jan. 21, 1999 issue of the New England Journal of Medicine. There, researchers at the University of Massachusetts Medical School reported that a man, who had received nef-deleted HIV-1 accidentally during a transfusion more than 15 years ago, has experienced a significant decline in CD4+ T cells--crucial components of the immune system. Drop-offs in these T-cell counts are an early warning sign of AIDS.
The second report comes from Australian researchers studying a group of people who had also been accidentally transfused with blood containing nef-deleted HIV-1. At the 12th World AIDS Conference last year in Geneva, Switzerland, the researchers reported that several of these people had experienced declines in CD4+ T cells.
"These results support our statements, going back to 1995, that human trials of vaccines with live nef-deleted HIV-1 should not proceed," Ruprecht says.
Co-authors of the study include Timothy Baba, M.D., Ph.D., of Dana-Farber, Harold McClure, D.V.M., of the Yerkes Regional Primate Research Center in Georgia and researchers at the Tulane Regional Primate Center in Louisiana and at Massachusetts General Hospital. Funding for the project was provided by the National Institute of Allergy and Infectious Diseases.
Dana-Farber Cancer Institute is a principal teaching affiliate of Harvard Medical School and is one of 35 federally designated Comprehensive Cancer Centers in the United States and one of 12 Centers for AIDS Research
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CONTACT: Dana-Farber Cancer Institute Todd Ringler, 617/632-5357
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