A LIVE HIV vaccine that can't infect the people it's supposed to protect may be possible after all. A team based in California has created a hybrid of HIV and another virus that can enter cells, but can't replicate once it's there.
The vaccine, containing four HIV genes surrounded by the coat of the vesicular stomatitis virus, should encourage the immune system to seek out and destroy cells harbouring HIV. Animal tests are due to start any time now. "The monkeys are all lined up and we're ready to go," says the team leader Flossie Wong-Staal, director of the Center for AIDS Research at the University of California in San Diego.
The treatment relies on priming den-dritic cells, which act as the gatekeepers of the immune system by spotting invading organisms and abnormal cells such as those from tumours and engulfing them. Dendritic cells display protein fragments of their "prey" on the surface, and this trains other components of the immune system such as T cells to recognise and destroy the same invaders or diseased cells.
Wong-Staal's plan is to extract dendritic cells from the patient's blood and infect these cells with the gutted HIV. The patient would then be injected with the treated cells to encourage their immune system to destroy HIV-infected cells. A similar technique has shown promise in treating skin cancer (New Scientist, 3 June, p 21).
Using real HIV, even in a severely weakened form, would be far too risky. So Wong-Staal and colleagues have removed the genes HIV needs to replicate itself, and added genetic material from the other virus.
They are treading cautiously, as previous attempts to develop an emasculated version of HIV ended in failure when the virus recovered its capacity to cause disease (New Scientist, 4 October 1997, p 5). The new hybrid "is one step away from the virus itself," says June Kan-Mitchell of the Karmanos Cancer Institute in Detroit, Michigan, who has been working closely with Wong-Staal. "These things can't replicate, but they are infectious, although only for one round of infection," she says.
Initial results of laboratory tests, due to appear in Blood next month, suggest that dendritic cells exposed to the vaccine encourage other components of the immune system to destroy cells infected with real HIV. "It's the first step to establishing the efficacy of the vaccine," says Kan-Mitchell.
Other vaccine researchers think the approach has potential. Ruth Ruprecht of Harvard Medical School agrees the vaccine should be safe because, unlike the live, attenuated vaccine her team has studied, Wong-Staal's virus can't replicate. She says she will watch progress of the trial closely. "It looks like an interesting approach and has potential," she says, although some scientists think that to protect against HIV, a vaccine will also need to generate antibodies (New Scientist, 11 March, p 16).
If Wong-Staal's strategy proves successful, either by itself or as part of a combined vaccine, the researchers hope that further development will allow the hybrid virus to be delivered directly to dendritic cells without having to remove them from the body first.
Author: Andy Coghlan
New Scientist issue: 17th June 2000
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