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May 05, 2010

Scientists Make Strides Toward AIDS Vaccine

Scientists have discovered why some people who are infected with HIV progress to AIDS very slowly, if ever.  They possess a gene that produces a potent immune response that keeps the infection at bay.  Researchers say their finding might someday lead to an AIDS vaccine.

About one in 200 people infected with HIV are so-called elite controllers, HIV-positive people who do not progress to AIDS, even without drugs, after many decades of being infected with the virus that causes AIDS.

Researchers have identified a protective mechanism produced by a gene called HLA-B57 that is found in elite controllers.  

The gene produces large numbers of immune system T cells, a type of infection-fighting white blood cell,  that latch on to cells that have been taken over by HIV, including mutated copies of the virus, and contain the damage caused by the disease.

Once activated, the programmed T cells also scour the rest of the body for other HIV-infected cells and kill them.

In previous research, scientists identified another gene in elite controllers called HLA-B27.  The presence of either gene seems to stave off AIDS in people infected with HIV.

Chemical engineer Arup Chakraborty, at Massachusetts Institute of Technology, developed a computer model of T cell development though the thymus, an organ behind the breast bone that conditions immune cells to recognize infections.

"Our findings suggest that the T cells that pass and come out of the thymus in people with HLA-B57 or HLA-B27 tend to be able to bind more strongly to strains of HIV that are infecting strains as well as mutants that emerge.  So their T cells repertoires are somewhat different," said Chakraborty.

A study of nearly 2,000 HIV infected patients - with and without the HLA genes - confirmed that those who lacked the genes did not have the immune system brake and they progressed to AIDS.

Scientists discovered the effect of elite controllers in HIV-positive patients during the late-1990s.  Since then, they have been trying to identify the immune system component that shields elite controllers from AIDS, so they can develop a vaccine.

Leading efforts to understand this rare group of HIV-infected people is Bruce Walker, an AIDS researcher at Harvard University and Massachusetts General Hospital, and co-author of the study.

Dr. Walker says the problem with developing a vaccine is that HIV is like a moving target, mutating rapidly after someone is infected and causing inevitable decline.

But Dr. Walker says the fact that the HLA-B57 and HLA-B27 genes control the virus, even as it mutates in some HIV-positive patients, might make an AIDS vaccine a reality.

"I think the fact that there are people out there that can be infected with HIV and successfully control it for decades tells me that this is a virus that we can get the upper hand with.  And I think this is a solvable problem," he said.

However Dr. Walker cautions that an AIDS vaccine is at least a decade away.

An article describing the genetic mechanism that slows progression of the AIDS virus is published this week in the journal Nature.