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WHEN the immune system goes wrong and begins to attack the body’s own cells,
the result can be devastating diseases such as rheumatoid arthritis, multiple
sclerosis and Crohn’s disease. But now a team of US researchers is proposing to
trick the body into launching an autoimmune response as a way of blocking HIV
infection. The new technique could circumvent the problems vaccine developers
have found when they try to target the AIDS virus, and it may also be a useful
way to treat other diseases.

The researchers discovered that if you stick a human protein on a virus, the
body won’t recognise it as one of its own. Instead, it will create antibodies
against what it thinks is a viral protein, says John Schiller of the National
Cancer Institute near Washington DC. Using this strategy, Schiller’s lab has
persuaded monkeys to produce antibodies against CCR5, a protein on the surface
of human cells that HIV latches on to.

Other studies had suggested that blocking CCR5, a co-receptor for CD4, could
be an effective strategy against HIV. People with two faulty CCR5 genes seem to
be much less likely to become infected with HIV, and take longer to develop AIDS
if they do. And people don’t seem to come to any harm when their CCR5 receptors
are disabled, says Edward Berger of the National Institute of Allergy and
Infectious Diseases near Washington DC. “There is real interest in the idea of
using antibodies against CCR5.”

Doctors already inject patients with manufactured antibodies to treat
diseases such as psoriasis, arthritis and Crohn’s disease. But the body clears
these antibodies within hours or weeks, so people need repeated injections.
Schiller was looking for a way to get the body to manufacture antibodies against
itself. Sometimes, a virus protein that resembles a human one can trigger an
autoimmune disease. So he wondered if he could use a virus to deliberately
induce an autoimmune response.

His team used a vaccine of virus-like particles made from the outer shell of
the human papilloma virus with mouse CCR5 on its surface. Last year they
reported that the mice given this vaccine generated antibodies that bound to
their own CCR5 receptors. In cell studies, these antibodies blocked HIV (
Proceedings of the National Academy of Sciences, vol 96, p 2373).

The next step was to try a similar experiment in macaques. A virus particle
“decorated” with macaque CCR5, which is homologous to CCR5 in humans, produced
fairly high levels of antibodies against the monkeys’ own CCR5. Next, the team
wants to try infecting the monkeys with an HIV-like virus to see if the CCR5
antibodies will protect them. “If we can do it in macaques, then the chances
that it won’t work in humans are small,” Schiller said last week at a vaccine
research meeting in Washington DC.

However, James Marion—a physician at the Mount Sinai School of Medicine
in New York who has used antibodies to treat Crohn’s disease—has
reservations. “My concern would be if you knock [CCR5] out, there might be a
price to pay. We’re really tinkering with pretty murky processes.” But CCR5 may
be a special case: neither the mice nor the macaques in Schiller’s experiments
showed any ill effects. “They’ve gotten some interesting findings,” says Berger.
“Let’s see if they get it.”