November 13 (HealthDay News) -- The latest attempt to develop an AIDS vaccine has failed, but researchers report that they've still gained insight into how to make the next one more effective.

"It's raised a whole new set of questions that are going to be really important to answer to get us to a successful vaccine," said Dr. Susan P. Buchbinder, lead author of a study published online Nov. 13 in The Lancet. "We couldn't have raised them or even anticipated them before doing this study."

Among other things, researchers now know that they need to understand the role of the foreskin in HIV transmission because uncircumcised men who were vaccinated had a higher rate of infection, said Buchbinder, director of the HIV research section at the San Francisco Department of Public Health.

Scientists have long dreamed about creating a vaccine to prevent transmission of HIV, the virus that causes AIDS. But the disease has turned out to be extremely stubborn. Among other things, HIV's ability to mutate into new forms has made it difficult to develop a vaccine that can keep up with all the changes.

Two experimental HIV vaccines have made it to testing in large numbers of people, but both failed to work.

In their study, Buchbinder and her colleagues looked at the results of testing of the second vaccine, which was developed by Merck & Co. Some of the results have already been released.

Researchers enrolled 3,000 HIV-negative people from North America, South America, the Caribbean and Australia in the study. Some received doses of the vaccine while others got a placebo.

The researchers found that 4.6 percent of those who received the vaccine became infected with HIV, compared to 3.1 percent of those who didn't get the vaccine.

It wasn't clear if the difference was statistically significant, but researchers did find that uncircumcised men were at higher risk of getting infected.

This suggests that scientists need to better understand how the foreskin affects the immune system's response to HIV, Buchbinder said.

Infection rates were also higher among those who had developed immunity to a virus that causes colds. This is important because scientists got the HIV vaccine to enter the body by piggybacking on a weakened bit of the same type of cold virus.

The vaccine can't cause HIV, and the weakened cold virus can't cause a cold, Buchbinder said.

But, there's another possibility, she said. The increase in infection rates among the two groups -- uncircumcised men and those who had immunity to the cold virus -- could be purely due to chance. Or some other factors could be at play.

The failure of the Merck vaccine "profoundly affected the HIV-vaccine development field," Dr. Merlin L. Robb, of the U.S. Military HIV Research Program, wrote in a commentary accompanying the study.

"We have learned that future HIV vaccines will need to generate stronger, broader or different types of immune responses in order to be effective," he said in an interview.

SOURCES: Susan P. Buchbinder, M.D., director, HIV research section, San Francisco Department of Public Health; Merlin L. Robb, M.D., U.S. Military HIV Research Program, Rockville, Md.; Nov. 13, 2008, The Lancet, online