Handful of 20-year HIV survivors hold key to discovering vaccine

Researchers are looking into the antibodies that provide natural immunity

Steve Connor
Sunday 15 March 2009 21:00 EDT
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In a desperate attempt to reverse 25 years of failure to develop an Aids vaccine, scientists have a new approach: studying people who have been infected with HIV for many years without any signs of ill-health. The patients' secret? Natural immunity.

The researchers have investigated the virus-fighting antibodies found in the blood of six long-term survivors of HIV whose own immune systems appear to be capable of shrugging off the virus. Results of tests show that a prototype vaccine made from several of the antibodies produced by those long-term survivors can prevent HIV from infecting human cells. The experiments have been successful on human cells growing in a test tube. Now further trials are planned on laboratory animals and human volunteers.

The search for an Aids vaccine has suffered a series of setbacks over the years. The most recent was the failure of the most promising potential vaccine, in a major clinical trial by the US drug company Merck. The trial, which had involved thousands of volunteers, had to be abandoned at the end of 2007 because of fears that the trial vaccine might in fact make patients more susceptible to Aids.

The results of the latest study, published in the journal Nature, come from the most preliminary stage of vaccine development. However, the scientists are optimistic that studying the natural immunity of long-term HIV survivors will eventually lead to a vaccine – something which is seen as the only effective way of controlling a global epidemic that kills about two million people a year.

Professor Michel Nussenzweig of The Rockefeller University in New York said the new approach is based on nature's way of fending off HIV, with antibodies produced by the human body itself, rather than trying to stimulate immunity with the more synthetically-produced "magic bullet" antibodies used in conventional Aids vaccines – which have all failed.

Long-term survivors of HIV have been known to live for 20 years or more without taking anti-viral drugs or even without showing any of the recognised symptoms of Aids, such as the fall in the number of certain white blood cells attacked by the Aids virus. It is thought that they can do this because they are born with an HIV-resistant immune system.

Professor Nussenzweig said the immune systems of these rare patients – who may represent just one in every 1,000 people infected with HIV – produce a set of antibodies that collectively are able to "neutralise" the virus, preventing it from infecting the blood cells of the immune system that it needs to replicate itself. "We wanted to try something different, so we tried to reproduce what's in the patient," said Professor Nussenzweig.

"And what's in the patient is many different antibodies that individually have limited neutralising ability but together are quite powerful. This should make people think about what an effective vaccine should look like.

"So here's a way of copying what exists in nature and that we know can work because of the long-term survivors. Instead of inventing something that doesn't exist, it's trying to copy something that does exist."

The scientists identified about 500 antibodies produced by these long-term HIV patients and used genetic techniques to mass produce them in the laboratory before testing them on live HIV and human cells in test-tube experiments.

Kai Brothers: 'My immune system is stable with no anti-virals'

Few people can say they have been infected with HIV for three decades without any ill-effects and ever having to take anti-viral medication. Kai Brothers is one of the lucky few, writes Steve Connor.

When Mr Brothers, who lives in San Francisco, first learnt that he was HIV-positive in the 1980s, he quit his job, spent his life savings and waited to die. Now, at the age of 46, he fully expects to live a normal life-span.

Like so many gay men of his generation, Mr Brothers has seen close friends die of Aids – including his own partner.

Although he is aware that he could infect others, Mr Brothers does not have to swallow a daily cocktail of anti-retroviral pills. Even though he did not take part in the latest study into long-term survivors, Mr Brothers said that his medical history is very similar to those who did. "HIV for 28 years, no progression to Aids and my immune system is stable with no anti-virals or meds of any kind," he said.

Some people are known to succumb to HIV within a few years of infection, others are able to cope for much longer without having to turn to drugs. But a few – and perhaps as few as one in 5,000 – may have natural immunity to HIV.

Mr Brothers appears to be one of those people lucky enough to be born with an immune system that can fend off HIV.

"I have been in studies drawing my blood monthly for 10 years now... I feel dedicated to giving back something because of my good fortune."

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