Washington DC
DOCTORS who have made headlines around the world by volunteering to be
injected with a controversial AIDS vaccine could be facing much bigger dangers
than they realised.
The vaccine consists of a live but weakened form of HIV that was thought to
be incapable of causing disease鈥攅xcept possibly in newborns. But
unpublished research now suggests that the vaccine could also cause AIDS in
adults.
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Leaders of the International Association of Physicians in AIDS Care (IAPAC),
based in Chicago, met officials of the US National Institutes of Health last
week to discuss their plan to act as human guinea pigs in a safety trial of the
vaccine. Fifty volunteers, mostly healthcare workers, have stepped forward.
The 鈥渓ive attenuated鈥� approach to HIV vaccine development has been pioneered
by Ronald Desrosiers at Harvard Medical School鈥檚 New England Primate Center in
Southborough, Massachusetts. He has injected monkeys with attenuated SIV, a
closely related virus, and shown that they are subsequently protected against
AIDS when injected with intact SIV. The attenuated HIV that the doctors want to
test has three genetic deletions, including parts of a gene called nef
鈥攚ithout which the virus has trouble reproducing.
After their meeting with NIH officials, the doctors announced that they
intend to apply for the Food and Drug Administration鈥檚 approval to begin the
trial. But even as they were speaking, Ruth Ruprecht, a researcher at the
Dana-Farber Cancer Institute in Boston, released new data from experiments on
adult monkeys that cast serious doubt on the safety of the trial. 鈥淥ur results
were rather shocking. The deleted version of the virus can still cause AIDS,鈥�
says Ruprecht.
Previously, Ruprecht has shown that up to 90 per cent of newborn monkeys
exposed to attenuated SIV show signs of immunodeficiency. Desrosiers has argued
that this only occurs if the monkeys are given very high doses of the vaccine
(This Week, 21 June, p 7).
And even if an attenuated virus poses a risk to
newborn infants, which have poorly developed immune systems, it may still be
safe in adults.
However, Ruprecht has now found that one of 18 adult rhesus monkeys infected
two years ago with an attenuated SIV has developed AIDS. Another is showing
early signs of immune deficiency. The monkeys were exposed only to the
attenuated SIV, not the unmodified virus.
鈥淲eakening the virus鈥檚 ability to replicate is not a safe vaccine strategy,鈥�
says Ruprecht. She decided to release her results because she thought the
volunteers didn鈥檛 know the risks they were running.
But IAPAC鈥檚 leaders appear undaunted. 鈥淭o make a quick judgment of any
specific data would be inappropriate,鈥� says Gordon Nary, the group鈥檚 executive
director.
Even before Ruprecht鈥檚 announcement, others were criticising the doctors鈥�
plan. The critics include Anthony Fauci, director of the National Institute of
Allergy and Infectious Diseases near Washington DC, which runs most of the NIH鈥檚
AIDS research.
The trial 鈥渋s not going to answer the substantial questions that need to be
asked鈥�, says Fauci. Even if it showed that the volunteers remained healthy for a
year or so, there is no guarantee that the attenuated virus will not cause
problems in the longer term. Fauci says more work has to be done with animals
before scientists can tell whether a human trial is justified.