Scientists announced the news today that many had all but given up hope of hearing: a drug trial in Thailand had shown that an experimental vaccine could protect against HIV/Aids, even if only to a limited extent.
Few expected the Thai trial to succeed, following as it did more than a decade of disappointment in the search for a vaccine culminating, in the failure two years ago, of a product made by the drug company Merck which looked much more promising.
But in a surprise outcome, the Thai trial conducted by the US army and the Thai ministry of public health found that a combination of two drugs afforded a 31% protection against HIV infection. The result was even more surprising as the two vaccines used in combination, Alvac and AidsVax, had not proven effective on their own. AidsVax flopped in trials in the US and also when it was given to 2,500 drug users at risk of HIV infection in Thailand.
Of the 16,000 male and female HIV- negative volunteers who took part in the biggest-ever Aids vaccine trial, half were randomly assigned the combined vaccine and the other half a dummy injection.
All participants had been counselled about protecting themselves and given condoms and treatment for sexually-transmitted infections to reduce their chances of picking up the virus. Of the first group, 51 were infected. Of the second, 74 became HIV-positive.
The immediate reaction from Aids scientists and campaigners came like a shriek of joy. "This is the first HIV vaccine candidate to successfully reduce the risk of HIV infection in humans," said Lieutenant General Eric Schoomaker, the US army's surgeon general. "We are very excited and pleased with the outcome of this trial and congratulate all those who participated in it."
"This is a historic day in the 26-year quest to develop an Aids vaccine," said Dr Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, an alliance of research organisations and funders including the Gates Foundation. Warren Mitchell, executive director of the Aids Vaccine Advocacy Coalition, called it a historic milestone.
"There is little doubt that this finding will energise and redirect the Aids vaccine field," he said.
But all recognised the enormous amount still to do if a promising trial result is to be turned into a routine vaccination. Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in the US, which part-funded the trial, said he was surprised and pleased by the outcome, but warned it was "not the end of the road". "It gives me cautious optimism about the possibility of improving this result," he said.
The trial has shown evidence that a "prime boost strategy", one vaccine followed later by the other, using two vaccines made of synthetic fragments of HIV based on subtypes B (common in the US and Europe) and E (common in Thailand and southeast Asia) can work. The full results will be presented at an Aids vaccine conference in Paris next month.
The big unanswered question is why it happened, how the two vaccines together can work where singly they do not.
"Now we need to understand how some of the participants in this trial were in some way protected," said Robin Shattock, professor of cellular and molecular infection at St George's, University of London. "It is essential to discover how this experimental vaccine affected the immune response of the participants.Once we understand what worked we can build on that to develop more effective vaccines."
Dr Jasmina Saric of the department of biomolecular medicine at Imperial College London said the combined vaccines seem to work on "a molecular weak point" of the virus. She said a more protective vaccine would have to be combined with existing prevention efforts.
The trial was launched in 2003, amid more hope than expectation. In 1997, President Bill Clinton had called for a commitment to develop an Aids vaccine within the next ten years, but the road had been nothing but rocky. Although donors such as the Bill and Melinda Gates Foundation and governments including the UK's put in substantial sums of money, researchers seemed to end up in blind alleys and trials ended early or had negative results.
The next steps are more analysis, more research and more trials. If efficacy had reached more than 50%, the vaccine combination would have been submitted to the Thai authorities for a licence. There is some way to go yet, and much to do if the approach is to be adapted to make a vaccine that works in Africa, where the strain is different and the need is greatest. The Alvac and AidsVax approach may not, in the end, be the vaccine that saves the planet from Aids, but this is one step further to one that will.