HOPE FOR AIDS VACCINE

Twenty six years after Luc Montagnier and Francoise Barré-Sinoussi identified the HI virus in Paris, a thousand scientists shared their knowledge last week on how to outsmart it.

An effective vaccine must teach the body to recognise and defend itself against the HIV, which is why scientists need to understand both how HIV infection and human immunity work.

“We need to know what immune response to induce in the body to get protection against HIV,” Barré-Sinoussi , co-winner of the 2008 Nobel Prize for Medicine, told the AIDS Vaccine Conference.

While scientists admit that they’re in need of “out-of-the-box ideas”, there are some promising signs.

There is finally evidence from a large Thai trial that it is possible for a vaccine to stimulate the human immune system to protect itself against HIV. Until a month ago when the results were first released, candidate vaccines had only worked on monkeys.

The Thai trial involved 16,400 Thai volunteers aged between 18 and 30 years. Half were given the vaccine and the other half a placebo.

They were all followed for three years, and 51 of those who got the vaccine became infected with HIV while 74 of those who had the placebo got HIV.

“This showed a modest protection of 31,2 percent,” Dr Supachai Resks-Ngarm from the Thailand Ministry of Health told the conference.

Resks-Ngarm added that there were no differences in gender, age, marital status or same-sex relationships between volunteers in the two arms of the trial that could have influenced the different infection rates.

While the trial, completed a month ago, only had a modest protective effect, it has given vaccine researchers a much-needed morale boost.

The priority for virologists in coming months is to find out exactly how the Thai vaccine worked, according to Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID).

Another promising sign is evidence that some people at high risk of HIV — such as a group of sex workers being studied in Kenya — are able to resist infection.

Others infected with HIV – “elite controllers” — are able to control their infection, keeping the level of virus in their blood (viral load) very low for years. These people have strong immune responses and are able to produce antibodies that neutralise HIV.

Scientists are studying how their immune systems work to see whether they can base a vaccine on stimulating what their immunes systems do.

What complicates HIV vaccine research is twofold: the virus makes frequent mistakes when it copies itself, meaning that it mutates (changes its structure) frequently. People infected with HIV for six years have more variations of HIV just inside themselves than all the variations of influenza currently found in the world.

The other complication is that HIV’s target is the immune system. Unlike other diseases, with HIV the very cells that are supposed to protect the body are the ones that become infected. So the cells that a vaccine would usually stimulate to fight infection are the ones that are falling sick and dying.

“With few exceptions, the disease is relentlessly progressive and virtually no one recovers spontaneously. The virus is never ultimately cleared and eradicated,” adds Fauci, who is one of the world’s giants in AIDS research despite his humble demeanour.

The latest vaccine research has honed in on three main things:

• The search for human antibodies that can neutralise HIV, and how these work.
• How HIV infection works in the mucosal system (vagina, gut, anus) where the virus first enters and infects the body.
• The most effective ways to deliver the vaccine into the body.

But Dr Alan Bernstein, head of the Global HIV Vaccine Enterprise, urged scientists to take more risks in research:

“Much of AIDS work discourages risky behaviour, but we need to take some risks to understand the virus better.”

There are currently around 24 trials underway, according to International AIDS Vaccine Initiative (IAVI). But all are still safety trials. None of them are in the all-important Phase 3, which is when the actual testing of the product takes place on a large group of people.

Dr Jerald Sadoff is a small plump man given to expressive hand gestures. He has been involved in vaccine research for 30 years and 10 of the vaccines he has worked on have been licensed.

“Products fail, not clinical trials,” says Sadoff. “You ask a question, you get an answer. You can’t be scared of failure. We tried 13 times before the cholera vaccine we were developing worked. There were 20 failures with malaria before the trial that is going on at the moment.”

There is broad consensus that the world will never be able to treat away HIV, only prevent it – and a vaccine is the most effective means of doing so.

“Condoms prevent HIV but you have to use them every time, so that makes them very ineffective as a public health initiative. A vaccine has to be given once so that makes it very effective,” asserts Sadoff.

Dr Katherine Kripke of the US NIAID echoes Sadoff: “Failure is part of the scientific process. It took 105 years to develop the typhoid vaccine, 47 years the polio one. The fastest one has been Hepatitus B which took 15 years.”