Hopes dashed for AIDS vaccine; science returns to basics August 3-8 in Mexico City (Feature)

By Pat Reber Jul 29, 2008, 5:20 GMT

Washington - The writing had been on the wall for some time.

But last week, it became official.

The search for a vaccine against HIV, the virus that causes AIDS, is taking an about-turn, back to the laboratory and away from human trials that had held out so much hope in the past two years.

The news was delivered by Dr. Anthony Fauci, the man whose US government institute controls about 80 per cent of the money spent worldwide on vaccine research and testing.

It came just in time to add a sobering note to the international AIDS community as it gathers for its biennial conference in Mexico City from August 3 to 8 and grapples with the disappointing news.

Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID) who will attend the conference, explained the decision in an interview with Deutsche Presse-Agentur dpa and talked about 'bringing expectations down to realistic levels.'

We have to understand how difficult the situation is and not expect that ... tomorrow we're going to start a large vaccine trial and we're going to get the answer in a couple of years,' he told dpa. 'It is extremely unlikely that that will happen.'

Before the 2006 conference in Toronto, hopes soared for two unconventional vaccines - the private Merck pharmaceuticals vaccine as well as NIAID's own PAVE vaccine, which was very similar to the Merck substance - as they headed into expanded clinical trials on human beings.

But Merck dropped testing in September 2007, and Fauci pulled the plug on the PAVE trials in mid July. The Merck vaccine was found ineffective, and in fact appeared to have inadvertently increased the HIV infection rate.

NIAID had backed development of the two unconventional vaccines after two decades of frustration over the failure to find one that worked along traditional lines.

The traditional approach to vaccines - using parts of the live virus to induce antibodies and thus immunity on exposure, without causing the illness - has not worked with HIV because the virus has an astonishing ability to change and disguise itself from the body's defences.

With HIV, the presence of antibodies does not protect against the disease.

The PAVE and Merck vaccines attempted instead to cause a cellular immune response that programmed the body's T-cells to search out and kill virus-infected cells. The goal was to reduce the HIV count in the body if the recipient became infected, slow down the progression of the disease and reduce transmissibility from an infected person - without expecting to totally eliminate the virus.

Fauci said the disappointing experiences with the alternative vaccine demonstrated the need to 'rev up the burners' and return to the laboratory to find how to create antibodies against the disease without causing an actual infection.

That means less money will be spent on human trials of vaccines that work in less conventional ways and more on animal testing, Fauci said.

'It isn't that we're going to completely stop and turn around 180 degrees, but we're going to torque or turn the knob on the system much more toward asking and answering some of the fundamental basic questions that we have not been able to answer up to now,' Fauci said.

The shift in focus follows intense discussion about downplaying expectations within the AIDS research community. Scientists are even annoyed by the rising pressure from the AIDS-affected community for faster progress.

Seth Berkley, president and founder of the New York-based International AIDS Vaccine Initiative (IAVI), cynically noted in the Wall Street Journal recently that an AIDS vaccine would probably materialize long before 'scientists discover a way to inoculate against the kind of unrealistic expectations that have induced much of the negative noise around the endeavour of late.'

Wayne Koff, a top IAVI researcher, told dpa that the field is still 'in the early stages of vaccine development' and in the past several years has gone through a 're-evaluation, a resetting of expectations.' But he noted that the consortium searching for the elusive antibody connection has immeasurably contributed to the knowledge base.

Scientists have learned for example 'exactly where and how' the antibodies attach onto the virus. Stimulating those antibodies to neutralize the broad variety of viruses is the next step.

IAVI says the 700 million dollars spent worldwide on vaccine research and testing every year is inadequate, and has been calling for the sum to be pushed to 1 billion dollars.