Search for new Aids vaccine guinea-pigs

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WANTED: healthy men and women who are not at risk of Aids but who are prepared to be injected with bits of HIV. It is not a job for the faint-hearted, but volunteers can content themselves with knowing they could be helping scientists develop the first effective Aids vaccine.

Later this year a team of Oxford University researchers want 40 people to offer their immune systems to medical science. Each will be injected with a new type of genetic vaccine developed from the DNA of the Aids virus.

It is the latest in a series of attempts to discover what some sceptics have described as an impossibility - an effective vaccine against HIV infection. Worldwide there are about 25 Aids vaccines under development yet none has shown any strong evidence that it will work against all but a few strains of HIV. This one just might.

The new approach is the brainchild of Andrew McMichael, an immunologist at Oxford's Institute of Molecular Medicine, who will be one of the first scientists to combine DNA vaccines against Aids with a more conventional approach based on the same vaccine used to immunise people against smallpox.

The 40 volunteers are needed as part of the first of three phases of clinical trials which will culminate in the immunisation of thousands of people at risk of Aids in Kenya. Some 1.5 million there are thought to be infected with HIV.

First, however, the vaccine has to be tested on a small number of healthy people who are at low risk of being infected with HIV, Professor McMichael said. "Volunteers must not look at this as a way of protecting themselves against HIV, because that would imply risk," he said. "Some will volunteer out of altruism; some may have relatives who are infected. They won't be paid, apart from expenses, and they'll have to come and give blood regularly for several months."

The aim of the initial trial is to assess the vaccine's safety. Professor McMichael said all the tests performed so far have shown it to be safe. However, every volunteer will be asked to sign a consent form acknowledging they are aware of the risks.

After more than 10 years of vaccine research there are worries about ever producing one that is effective against one of the fastest mutating viruses known to science. What makes the Oxford approach unique among the vaccine candidates is the combination of old and new techniques designed to raise the antibodies needed to prevent HIV gaining a foothold.

Volunteers will be injected with "naked" DNA composed of bacterial genes interwoven with an HIV gene that is responsible for making one of the virus's core proteins.

If all goes to plan the DNA vaccine will be taken up by the volunteer's cells which will then manufacture the virus's core protein. This should stimulate the body's immune defences to recognise the protein as an foreign "antigen" which its own antibodies can then attack. Once done, the second stage is then brought into play. This involves injecting the volunteers with a vaccinia virus used to inoculate against smallpox, which had been genetically engineered to produce HIV proteins.

By exposing the body's immune system to HIV through two different routes, scientists hope it will be prepared to deal quickly with a genuine infection.

"If we can get the immune response that I think we can get, we'll get some sort of effect. We have a chance of getting there, but we don't know until we try it," Professor McMichael said.