IN THE context of Africa鈥檚 catastrophic AIDS epidemic, the infection of six
Kenyan women with HIV may seem like just another series of personal tragedies.
But the news has dismayed leading researchers and may send a team working on one
of the most promising approaches to an AIDS vaccine back to the drawing
board.
The women, formerly prostitutes, are special cases: despite repeated exposure
to HIV, their immune systems had seemed impervious to the virus. AIDS
researchers believed these women had beaten HIV infection once鈥攁nd in the
process had become immune. By taking lessons from the women鈥檚 unusual biology,
scientists in Oxford believed they had developed a vaccine to combat Africa鈥檚
AIDS epidemic
(快猫短视频, 28 November 1998, p 5).
Since 1985, the Oxford researchers, together with Canadian and Kenyan
scientists, have studied a group of 43 Kenyan prostitutes who had remained
HIV-free despite intensive exposure to a variety of HIV strains. The women all
have large numbers of special white blood cells known as cytotoxic T lymphocytes
(CTLs), which are primed to kill other cells in which HIV hides.
Advertisement
To stimulate a similar response, the researchers devised a vaccine consisting
of a small loop of DNA, called a plasmid, containing fragments from genes for
three different HIV proteins plus a live, disabled cowpox virus with the same
gene fragments added to its genome. In tests on monkeys, the vaccine stimulated
production of CTLs and protected against HIV infection.
But at a meeting of HIV specialists at St Thomas鈥檚 Hospital in London earlier
this month, Sarah Rowland-Jones of the University of Oxford announced that six
of the prostitutes, most of whom have now left the business, are now
HIV-positive. Describing the news as 鈥渄ismaying鈥�, she told the meeting that the
women鈥檚 immunity fell away once they were no longer being exposed to HIV on a
daily basis. 鈥淭his implies that to maintain immunity you need to have continual
别虫辫辞蝉耻谤别.鈥�
That鈥檚 bad news for a vaccine designed for the developing world, where health
budgets may not extend to repeated vaccinations. 鈥淭he implications are that the
vaccine will have to be given in multiple boosts, which will be more difficult
and expensive,鈥� says Paul Clapham, an HIV researcher at University College
London.
Nevertheless, the International AIDS Vaccine Initiative, which is sponsoring
the vaccine鈥檚 development, is not giving up hope. Jaap Goudsmit of the
University of Amsterdam, scientific adviser to the initiative, believes the
Oxford vaccine could prove useful as a component of a combined vaccine that also
stimulates the production of antibodies against HIV. 鈥淲e want as many approaches
as possible for phase I studies and then we can choose between them or mix and
match,鈥� he says. New evidence of the importance of generating antibodies in HIV
vaccination will appear in Nature Medicine next week.
Phase I safety trials of the Oxford vaccine will start this year in 30
British volunteers. If they go well, further safety trials will take place in
Nairobi, and within five years, this will be followed by a trial involving
hundreds of Kenyans.