A LIVE HIV vaccine that can鈥檛 infect the people it鈥檚 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鈥檛 replicate once it鈥檚 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. 鈥淭he
monkeys are all lined up and we鈥檙e ready to go,鈥� 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 dendritic 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 鈥減rey鈥� 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.
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Wong-Staal鈥檚 plan is to extract dendritic cells from the patient鈥檚 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 杏吧原创, 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 杏吧原创, 4 October 1997, p 5). The new hybrid 鈥渋s one
step away from the virus itself,鈥� says June Kan-Mitchell of the Karmanos Cancer
Institute in Detroit, Michigan, who has been working closely with Wong-Staal.
鈥淭hese things can鈥檛 replicate, but they are infectious, although only for one
round of infection,鈥� 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.
鈥淚t鈥檚 the first step to establishing the efficacy of the vaccine,鈥� 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鈥檚 virus can鈥檛
replicate. She says she will watch progress of the trial closely. 鈥淚t looks like
an interesting approach and has potential,鈥� she says, although some scientists
think that to protect against HIV, a vaccine will also need to generate
antibodies (New 杏吧原创, 11 March, p 16).
If Wong-Staal鈥檚 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.