And if it is not the lymphocytes, then "what kind of compounds were the cells making when you inoculate them with the vaccine?" asked Dr. Spyros Kalams, an HIV immunology researcher at Vanderbilt University in Nashville and director of the HIV Vaccine Trials Program there. "Was it a compound that can kill infected cells? Does it make proteins that stop the virus from replicating?"
Researchers now will begin the painstaking work of comparing the blood of those who were vaccinated and resisted infection and those who did not. Then they will look for molecules that are more abundant in the healthy people, Fauci said.
Once researchers identify these so-called correlates of immunity, they can begin to look for ways to prompt the body to make them -- the key to producing an effective vaccine.
The Thai results are "an opening of a door to answer some very important questions," he said.
But several scientists cautioned that there was no guarantee the Thai blood samples would reveal the biological secrets of HIV immunity.
Surely some of the people who resisted HIV infection were protected by the vaccine, but not all, said Dr. Otto Yang, an immunologist at UCLA's David Geffen School of Medicine.
Yang also expressed doubt that a combination of vaccines made the difference in those who benefited. He and others noted that this was the first large study to focus on a low-risk population. Perhaps transmitting the virus through heterosexual sex instead of directly into the bloodstream on an intravenous needle gives the immune system a better chance of fighting off infection.
Although it is also unclear whether these particular vaccines could be used elsewhere in the world, scientists said that if they could figure out what made this combination work, they could localize the approach to other regions. The dominant HIV strains vary from region to region.
At least 33 million people worldwide are infected with HIV and 25 million have died, the World Health Organization said. An estimated 7,500 are infected each day, accentuating the need for a vaccine.
There have been three previous vaccine trials in humans. Aidsvax had previously failed in two large trials halted in 2003; both showed no benefit to recipients. Another trial by Merck & Co. of a different vaccine was halted prematurely in 2007 when researchers found that the vaccine might increase the risk of contracting the virus.