Team finds clues to resisting HIV

A group led by Duke scientists spots genetic differences that might help create vaccines

Scientists have found clues to promising designs for HIV vaccines that might bolster natural immunity, expanding a line of attack desperately needed to slow the worldwide AIDS epidemic.

An international team led by Duke University scientists found genetic differences in people who appear better equipped naturally to resist HIV. These people get infected when exposed to the virus, but have some biological edge that lessens HIV levels in their bodies early on. Making less virus decreases a person's chance of infecting someone else and can slow the development of deadly AIDS.

The genetic finding is the first significant result from an international coalition of researchers that stresses cooperation over the usual competition in the quest to create HIV vaccines. Some compare the coalition to a non-violent Manhattan Project, the high-level 1940s scientific collaboration that cracked technological barriers to making an atomic bomb.

"I'm expecting very important things from this," said Anthony Fauci, a longtime AIDS scientist and director of the National Institute of Allergy and Infectious Diseases. The institute has committed $300 million to the Center for HIV/AIDS Vaccine Immunology, a prime player in the collaboration whose leadership is based at Duke.

Led by Duke scientist David Goldstein, the research published Thursday online by the journal Science will not produce medical therapies immediately. Scientists must first confirm that the genes are key to immune responses and, if so, unlock exactly how they boost HIV resistance. Then they must find ways to build that ability in others with a vaccine.

Probing DNA thickets

Even if these specific genes don't prove useful in an HIV vaccine maker's laboratory, the technique of hunting for biological differences in the thickets of people's DNA could turn up genes that finally crack the vaccine puzzle, said Dr. Mark Connors, a scientist at the National Institutes of Health not involved in the project who is familiar with the results.

To help with that effort, Goldstein and his collaborators also published descriptions of scores of gene variants that might have played a role in the patient's HIV immune responses, but didn't play a statistically significant role among the numbers of subjects in the genomics study.

"In science we are confined by what we already know," Connors said. "This is a kind of thing that takes a fresh look."

The genomics results are highly encouraging to scientists who hope that genomics can help fight AIDS, which has claimed 25 million lives worldwide since the 1980s. Genomics studies use vast amounts of genetic information to find variations in groups of people. This research is the first to apply that technique to people's immune response to an infectious disease.

HIV can be lethal because it disables people's immune systems and eventually blossoms into AIDS, which leaves people vulnerable to multiple, fatal illnesses. Scientists haven't yet figured out how to strengthen people's normal immune systems to destroy the virus, but they are still looking. They are also searching for ways to improve immunity enough to contain the virus.

"Some of these people control the virus so well that that it falls to undetectable levels," said Goldstein, director of Duke's Center for Population Genomics and Pharmacogenetics. "If we could understand why, maybe we could control the virus as well."

Vaccines on trial

Several HIV vaccines are already in clinical trials, although so far no single one is a silver bullet to stop the HIV virus, which infects nearly 40 million people worldwide. It may well be that one day public health workers will use more than one vaccine to try to stop or slow HIV's spread.