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The search for an AIDS vaccine was thrown into disarray last week with
the disclosure of ‘stunning’ findings from experiments on monkeys carried
out by Britain’s Medical Research Council. The results undermine earlier
studies on monkeys, which many considered crucial steps towards the development
of a human vaccine. Some researchers now think they should completely revise
their approach to understanding the way the body protects itself against
retroviruses, the family that includes HIV.

Å®ÉúСÊÓƵs have always assumed that the immune system protects itself
against HIV by making antibodies to the virus’s proteins. Theoretically,
these antibodies should stop the virus entering cells. But the new results
challenge these assumptions. In essence, they suggest that, however the
vaccines protect monkeys, it may not be by stimulating the production of
antibodies against viral proteins. Instead, the vaccines seem to rely on
stimulating antibodies to proteins from human cells. These cells are used
in the preparation of the vaccines.

‘I’m gobsmacked,’ said Jonathan Weber, professor of communicable diseases
at St Mary’s Hospital in London and the director of Britain’s only human
trial of a potential AIDS vaccine. Some scientists said the results were
‘incredibly disappointing’ and ‘a major setback’. Others said the numbers
were small and it was too early to judge the work’s significance. But the
scientists from the MRC, who announced the findings at an AIDS workshop
in Coventry last week, insisted that the discovery was exciting and could
open new research avenues.

Whatever the findings mean, they come at an awkward time for the MRC
team. There is serious disquiet among many British AIDS scientists about
what they see as an overemphasis on the study of monkeys in the MRC’s AIDS
programme. No one will speak out in public for fear of losing a grant, but
privately many scientists have criticised Geoffrey Schild, director of the
MRC’s AIDS Directed Programme, for this emphasis. One delegate at the meeting
said Schild’s leadership must now be in question. Another researcher said:
‘It’s pretty damaging. I think it was a good idea to have an AIDS Directed
Programme in the early days, but it may be time to re-evaluate the programme.’

But others defended the programme and its spending on monkeys. ‘These
findings prove there is a point to animal models,’ said Weber. ‘Although
this hiccup is extremely important it is better that it happened in animals
than in man.

Like many of the studies so far, the British experiment involved macaques.
These animals have their own equivalent of HIV, a virus called simian immunodeficiency
virus (SIV), which causes an AIDS-like disease. Because of this, many groups
have believed that macaques are a good model for developing AIDS vaccines.
About 100 macaques in the US and Britain have now been successfully immunised
against live SIV by vaccines based on preparations of whole, killed virus.

The MRC researchers gave four macaques a vaccine based on cultured human
T cells that had been infected with SIV and then inactivated. When they
gave these monkeys live virus, three out of four were protected. But the
shock came from four other monkeys. The researchers gave these animals uninfected
human cells of the same type as those used to create the vaccine. These
cells had never seen SIV. To the team’s amazement, when they gave the animals
live SIV, two of them were protected.

Next, the researchers examined the animals’ antibodies. The protected
animals had high levels of antibodies to proteins that came not from SIV,
but from the human T cells. Unprotected animals had only a tenth of the
level of these ‘anticell’ antibodies. This is the first time researchers
have been able to link the level of an antibody with the degree of protection
in macaques.

The team also studied antibodies from macaques used in previous vaccine
experiments. They found the same pattern of immune response in animals that
had received a vaccine based on killed SIV alone, without human cells. But
the vaccine had been cultured in human cells. Researchers know that proteins
from the cells can become incorporated into the virus.

Ron DesRosiers of the New England Regional Primate Center in the US
told New Å®ÉúСÊÓƵ that he was stunned by the news from Britain. DesRosiers,
who has done some of the most important vaccination studies with macaques,
added: ‘It calls into question the basis of all the previous protection
studies, including my own.’

Some scientists were angry that the vital control experiment with uninfected
cells had not been done earlier. But Jim Stott of the MRC countered that
the need for such a control was not obvious at the beginning, pointing out
that everyone tries to minimise the number of monkeys they use in experiments.
‘It’s terribly easy to say that afterwards,’ he said. ‘It would have been
such a bizarre experiment to suggest. You have to try to save animals.’
Stott is excited by the discovery. ‘Some people will view this negatively;
I think it is also opening things up. The new finding could turn out to
be very important, or it could turn out to be a lemon. That’s science.’

Å®ÉúСÊÓƵs have based most of their optimism about AIDS vaccines on
studies in macaques. About five champanzees have also been protected from
HIV infection. However, a larger number of chimpanzee experiments have failed.
Philip Berman of the biotechnology company Genentech in San Francisco, who
has succeeded in protecting champanzees with a vaccine based on a purified
form of HIV’s protein coat, said: ‘It’s not good for the whole field. It
was very helpful to have as many underpinnings as possible in this field.
Now one of those underpinnings has totally disappeared.’ However, one rumour
says that Genentech has since asked to work with the MRC team on SIV, indicating
that the company sees something useful in the findings.

About a dozen potential AIDS vaccines are being tested in people to
check safety. No one is ready to test whether a vaccine protects against
infections.