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Finding protection in AIDS virus fragments.

Finding protection in AIDS virus fragments

Separate studies in humans and chimpanzees show that injection of harmless fragments of the AIDS virus may one day protect people from the disease-causing agent.

Two chimpanzees vaccintated with gp120, a protein from the AIDS virus' outer coat, remain free of infection more than six months after subsequent injection with the deadly virus, report researchers from Genentech, Inc., in San Francisco. In contrast, a third chimpanzee exposed only to the AIDS virus (HIV) developed infection after seven weeks, notes molecular biologist Phillip Berman of Genentech. A full account of the work, conducted in collaboration with the Southwest Foundation for Biomedical Research in San Antonio, Texas, will appear in the June 14 NATURE, Berman says.

Researchers caution that the animal study demonstrates protection against only one of the AIDS viral strains. But the finding bolsters hope of one day using key protein fragments from the virus, which by themselves cannot cause the disease, to develop and AIDS vaccine, says virologist Alan M. Schultz of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., who coordinates the national AIDS-vaccine research effort.

A new study involving humans also supports the concept of developing an AIDS vaccine by inoculation with protein fragments. Robert F. Siliciano and his colleagues at the Johns Hopkins University in Baltimore, and MicroGeneSys, Inc., in West Haven, Conn., injected eight healthy human volunteers with gp 160, the protein precursor to gp 120 and another AIDS protein known as gp41. The researchers found that certain lymphoctyes cloned from three of the volunteers killed cells in vitro that had incorporated free-floating gp 160 placed in extracellular fluid. The "killer" cells in their study, Siliciano and his co-workers discovered, all belonged to a class of immune system cells known as CD4, named for a molecule on their surface that acts as the binding site for the AIDS virus.

That initial finding was not surprising, Siliciano says, because he and other researchers reported several years ago that CD4 cells -- generally believed only to assist other immune cells -- can kill virus-infected cells on their own, lysing those that have incorporated in antigen from outside the cell onto their surfaces. But the current study takes that research a major step further.

Siliciano and his collaborators report in the June 8 SCIENCE that seven of the 11 CD4 clones from the three human volunteers killed AIDS-infected cells. Five of the seven did not harm uninfected cells, while two killed uninfected cells incubated with gp 120 protein. All five of the protective clones generated by gp160 inoculation, he says, recognized the gp41 AIDS protein, but not the gp120. The finding, Siliciano adds, suggests that attempts to make an AIDS vaccine by inoculation with viral protein framents should include gp41 to yeild the best possible results.

The new work, Siliciano says, demonstrates for the first time that CD4 cells can be triggered to kill a cell that displays surface antigens produced inside the cell, rather than outside. The AIDS virus, he notes, produces the telltale gp120 inside cells it infects. When an infected cell places gp120 on its surface, CD4 cells from inoculated volunteers can kill the cell.

"These researchers have crumbled the orthodoxy that the only way to make an AIDS vaccine is with a live or attenuated virus," says Schultz. He adds that the protective effect of these clones gives encouragement that researchers can produce an AIDS vaccine without harming healthy cells.
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Author:Cowen, Ron
Publication:Science News
Date:Jun 9, 1990
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