WHEN the immune system goes wrong and begins to attack the body鈥檚 own cells,
the result can be devastating diseases such as rheumatoid arthritis, multiple
sclerosis and Crohn鈥檚 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鈥檛 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鈥檚 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鈥檛 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. 鈥淭here is real interest in the idea of
using antibodies against CCR5.鈥�
Advertisement
Doctors already inject patients with manufactured antibodies to treat
diseases such as psoriasis, arthritis and Crohn鈥檚 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
鈥渄ecorated鈥� with macaque CCR5, which is homologous to CCR5 in humans, produced
fairly high levels of antibodies against the monkeys鈥� 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. 鈥淚f we can do it in macaques, then the chances
that it won鈥檛 work in humans are small,鈥� Schiller said last week at a vaccine
research meeting in Washington DC.
However, James Marion鈥攁 physician at the Mount Sinai School of Medicine
in New York who has used antibodies to treat Crohn鈥檚 disease鈥攈as
reservations. 鈥淢y concern would be if you knock [CCR5] out, there might be a
price to pay. We鈥檙e really tinkering with pretty murky processes.鈥� But CCR5 may
be a special case: neither the mice nor the macaques in Schiller鈥檚 experiments
showed any ill effects. 鈥淭hey鈥檝e gotten some interesting findings,鈥� says Berger.
鈥淟et鈥檚 see if they get it.鈥�
