An experimental vaccine has prevented infection with the Aids virus for the first time, a breakthrough in the fight against the deadly illness.
The World Health Organisation and the UN agency UNAids said today the results "instilled new hope" in the field of HIV vaccine research.
The vaccine cut the risk of becoming infected with HIV by more than 31% in the world's largest Aids trial of more than 16,000 volunteers in Thailand.
Even though the benefit is modest, "it's the first evidence that we could have a safe and effective preventive vaccine", said colonel Jerome Kim who helped lead the study for the US Army, which sponsored it with the National Institute of Allergy and Infectious Diseases.
The institute's director, Dr Anthony Fauci, warned that this was "not the end of the road", but said he was surprised and very pleased by the outcome.
"It gives me cautious optimism about the possibility of improving this result" and developing a more effective Aids vaccine, he said. "This is something that we can do."
The Thailand Ministry of Public Health conducted the study, which used strains of HIV common in Thailand. Whether such a vaccine would work against other strains in the US, Africa or elsewhere in the world is unknown, scientists stressed.
Even a marginally helpful vaccine could have a big impact. Every day, 7,500 people worldwide are newly infected with HIV; two million died of Aids in 2007.
"Today marks a historic milestone," said Mitchell Warren, executive director of the Aids Vaccine Advocacy Coalition, an international group that has worked toward developing a vaccine.
"It will take time and resources to fully analyse and understand the data, but there is little doubt that this finding will energise and redirect the Aids vaccine field," he said.
The study tested the two-vaccine combination in a "prime-boost" approach, in which the first one primes the immune system to attack HIV and the second one strengthens the response.
They are ALVAC, from Sanofi Pasteur, the vaccine division of French drugmaker Sanofi-Aventis; and AidsVAX, originally developed by VaxGen and now held by Global Solutions for Infectious Diseases, a non-profit founded by some former VaxGen employees.
ALVAC uses canarypox, a bird virus altered so it can't cause human disease, to ferry synthetic versions of three HIV genes into the body. AidsVAX contains a genetically engineered version of a protein on HIV's surface. The vaccines are not made from whole virus - dead or alive - and cannot cause HIV.
Neither vaccine in the study prevented HIV infection when tested individually in earlier trials, and dozens of scientists had called the new one futile when it began in 2003.
"I really didn't have high hopes at all that we would see a positive result," Mr Fauci confessed.
The results proved the sceptics wrong.
"The combination is stronger than each of the individual members," said the Colonel Kim, a physician who manages the army's HIV vaccine programme.
The study tested the combo in HIV-negative Thai men and women aged 18 to 30 at average risk of becoming infected. Half received four "priming" doses of ALVAC and two "boost" doses of AidsVAX over six months. The others received dummy shots. No one knew who got what until the study ended.
Thanad Yomha, a 33-year-old electrician from south-eastern Thailand, said he did not expect anything in return for volunteering for the project.
"I did this for others," Thanad said. "It's for the next generation."
All were given condoms, counselling and treatment for any sexually transmitted infections, and were tested every six months for HIV. Any who became infected were given free treatment with antiviral medicines.
Participants were followed for three years after vaccination ended.
New infections occurred in 51 of the 8,197 given vaccine and in 74 of the 8,198 who received dummy shots. That worked out to a 31% lower risk of infection for the vaccine group. Two of the infected participants who received the placebo died.
The vaccine had no effect on levels of HIV in the blood for those who did become infected. That had been another goal of the study - seeing whether the vaccine could limit damage to the immune system and help keep infected people from developing full-blown Aids.
That result is "one of the most important and intriguing findings of this trial", Fauci said. It suggests that the signs scientists have been using to gauge whether a vaccine was actually giving protection may not be valid.
"It is conceivable that we haven't even identified yet" what really shows immunity, which is both "important and humbling" after decades of vaccine research, Fauci said.
Details of the $105m (€71m) study will be given at a vaccine conference in Paris in October.
This is the third big vaccine trial since 1983, when HIV was identified as the cause of Aids. In 2007, Merck stopped a study of its experimental vaccine after seeing it did not prevent HIV infection. Later analysis suggested the vaccine might even raise the risk of infection in certain men. The vaccine itself did not cause infection.
In 2003, AidsVAX failed two large trials - the first late-stage tests of any Aids vaccine at the time.
"This is a world first which proves that vaccine development is possible," said Dr. Supachai Rerks-Ngarm, the Thai Health Ministry official who oversaw the trial. "But this is not to the level where we can licence or manufacture the vaccine yet."
Mass-producing the vaccine, plus how to proceed with future studies, will be discussed among the governments, study sponsors and companies involved in the trial.
Scientists want to know how long protection will last, whether booster shots will be needed, and whether the vaccine helps prevent infection in gay men and injection drug users, since it was tested mostly in heterosexuals in the Thai trial.
The study was done in Thailand because US Army scientists did pivotal research there when the Aids epidemic emerged there, isolating virus strains and providing genetic information on them to vaccine makers.