Dormant DNA could be key to effective HIV vaccine: researchers
Last Updated: Friday, November 9, 2007 | 9:43 AM ET
The Canadian Press
Canadian and U.S. scientists have identified a potential new "Trojan Horse" method for creating a vaccine against AIDS, even as repeated efforts by researchers to prevent HIV infection using traditional immunization approaches continue to fail.
Instead of trying to directly target the rapidly mutating human immunodeficiency virus, the scientists suggest a vaccine could take aim at what's known as fossil DNA — genetic material from ancient viruses that has inserted itself into every human cell over our evolutionary history.
In a study published Friday in the journal PLoS Pathogens, the researchers say it appears that HIV reactivates this usually dormant DNA — called human endogenous retroviruses, or HERVs — by disrupting the normal controls that keep it in check.
In their study, the researchers looked at 29 people who were recently infected with HIV and compared them with 13 HIV-negative individuals and three others infected with hepatitis C but not the AIDS virus. In the group recently infected with HIV, they found a relationship between the degree of immune response to HERVs and the levels of HIV present in their blood.
In some HIV-positive individuals, the study found that infection-fighting T cells are able to target HERV-enabled cells, said co-principal author Brad Jones, a PhD candidate in immunology at the University of Toronto.
Jones said a huge stumbling block for scientists and drug companies seeking an effective vaccine is that HIV is like a moving target: it exists in many variations and constantly mutates.
"If we can find other ways for the immune system to target HIV-infected cells, we can overcome this problem in making an HIV vaccine," co-author Dr. Keith Garrison, a postdoctoral fellow in experimental medicine at the University of California, San Francisco, said in a statement. "HERV may provide us with a good target to test."
In the latest setback in the quest for an HIV vaccine, drugmaker Merck and Co. announced Wednesday that an experimental AIDS shot not only failed to work, but volunteers who got the injections were more likely to get infected with the virus through sex or other risky behaviours than those who got dummy inoculations.
Merck had already announced in late September that it was stopping its trial because the vaccine did not work, raising the question of whether that failure is a harbinger of a similar fate for a number of other AIDS vaccines now being tested.
Traditional vaccines work by stimulating immune system cells to seek out and destroy foreign invaders like bacteria and viruses. But because HIV is an extremely adaptable retrovirus, it is able to foil attempts by the immune system to shut it down.
In fact, it uses the body's own immune T cells as an incubator to make copies of itself, before spreading its progeny to other host cells.
Even if a traditional vaccine does elicit an immune response, "the virus may still be able to escape," Jones said. "So it may not matter how hard we hit it."
But because HERVs are already part of our genetic makeup, they are virtually unable to mutate, he said. "So there's a great advantage in that in targeting HERV."
That's where the Trojan Horse idea comes in: HIV activates HERVs within the cell it enters, so a vaccine that takes aim to destroy HERVs will incidentally kill HIV and stop it from jumping to other cells, the researchers said.
