A Thai and American team had announced early Thursday in Bangkok that they had found a combination of vaccines that provided modest protection against infection with HIV, offering the first proof of principle that the deadly disease could be tamed by teaching the immune system to recognize the virus and defeat it.
But by Thursday afternoon, the initial wave of euphoria had given way to the recognition that many vexing questions will have to be answered before researchers can produce a vaccine that will reliably shield people from HIV.
For starters, it could take years to unravel the biological mechanisms that produced the apparent 31% reduction in infections among those given the vaccine regimen.
Researchers have never before observed antibodies or other molecules in the blood that could block an infection of HIV, the virus that causes AIDS. Now they will try to figure out whether this combination of vaccines stimulated new molecules, or provoked an unusual blend of ones previously observed.
Experts predicted that it would require two to three years of research to better understand how the vaccine worked, and an additional five to 10 years to produce a vaccine that was ready to test in people.
Some researchers even wondered whether the apparent reduction in infections was simply a statistical fluke resulting from the small number of HIV cases observed in the trial.
The abundance of unanswered questions hasn't sapped the enthusiasm of many HIV researchers. After 26 years of seemingly futile research on vaccines, they have finally made some progress on demonstrating the feasibility of an HIV vaccine, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which largely funded the $120-million study.
"This is the first positive signal -- modest though it may be -- that we have ever gotten with any vaccine that we have ever tested in humans," Fauci said. But "is it a vaccine that is ready for prime time? No."
The Thai trial, which began in 2003, had been disparaged by many critics as a waste of time and money because its two vaccines had produced no benefit in individual trials. But a few researchers speculated that using them together -- with one vaccine priming the immune system and the second boosting that response -- would be more effective.
The primer in this combo is Alvac, made by Sanofi Pasteur, which uses a defanged canarypox virus to carry three synthetic HIV genes into the body. The boost comes from Aidsvax, originally made by VaxGen Inc. and now owned by the nonprofit group Global Solutions for Infectious Diseases. It contains a genetically engineered version of a protein from the HIV surface.
The study, led by Dr. Supachai Rerks-Ngarm of the Thai Ministry of Public Health's Department of Disease Control, involved more than 16,000 volunteers in Thailand, all from the general population rather than from a pool of high-risk homosexuals and intravenous drug users used in past studies. Half received four priming doses of Alvac and two boost doses of Aidsvax over a six-month period; the other half received placebo shots.
After three years of follow-up, new HIV infections were observed in 74 of the 8,198 people who received the placebo, but in only 51 of the 8,197 given the vaccine, a statistically significant 31% reduction.
To the researchers' disappointment, however, the vaccine did not reduce levels of HIV activity in those who became infected after being vaccinated.
The trial was carried out in Thailand because the initial research was conducted there and the vaccine was based on the version of HIV that circulates in that country.
Full details of the study will be released next month at a conference in Paris, and researchers are eagerly awaiting them.
Dr. Salim S. Abdool Karim, an epidemiologist at Columbia University in New York and director of the Centre for the AIDS Programme of Research in South Africa in Durban, said he was particularly eager to know whether people who got vaccinated and stayed healthy had a bigger response from the white blood cells known as cellular T lymphocytes.
"A whole range of vaccines were developed on the hypothesis that they generated sufficient [cellular T lymphocyte] responses to either prevent infection or impact viral load," he said. "We've never been able to test that hypothesis because no vaccine has worked until now."