One year after a puzzling setback in the hunt for an AIDS vaccine, researchers say their defeats have forced them to look for entirely new ways of creating a defence against the disease.

After nearly 30 years, 25 million deaths and billions of dollars spent with no vaccine to show for it, scientists at this year’s international AIDS Vaccine Conference said they were turning to novel approaches to overcome their defeats.

“We are in the middle of quite a profound shift of mindset in the research community,” said Alan Bernstein, director of the Global HIV Vaccine Enterprise, an alliance of organisations working on a vaccine.

Speaking to AFP on the sidelines of the meeting that ended Friday in Cape Town, he said that startling setbacks had forced scientists to delve into sophisticated new research to tackle the disease.

Last year scientists were forced to abandon two advanced clinical trials of a vaccine by pharmaceutical company Merck, after it appeared to actually heighten the risk of AIDS infection.

“The Merck result was such a surprise and everyone was kind of knocked off their horses… What happened no one could have predicted,” Mitchell Warren of the AIDS Vaccine Advocacy Coalition said.

“They still don’t understand exactly what happened. That finding forces people to realign and look at new ways and new approaches to how we are going to find an AIDS vaccine because it was so surprising.” About 30 other clinical trials are underway around the world, but the most watched is a study in Thailand that began in 2003, with results expected next year.

That study is the biggest ever, with 16,000 people enrolled.

Scientists say that whatever the outcome, it will provide valuable information on the pandemic, which most agree won’t see a vaccine for decades.

Meanwhile, Warren says the failure of the Merck trial has already forced scientists to rethink their basic assumptions about how vaccines work.

“People are really grappling with new ways of doing things,” he said.

In the past vaccines have either caused the body to develop antibodies that kill a disease, or to attack infected cells to kill them off before a disease spreads.

But HIV mutates at every turn, making it almost impossible to design a vaccine to attack it.