Insight into HIV immunity may lead to vaccine

By investigating the action of the human antibodies called ADCC in people with HIV, researchers were able to identify that the virus evolves to evade or ‘escape’ the antibodies.

Professor Stephen Kent of the University of Melbourne and one of the senior authors on the paper said ADCC antibodies have been strongly implicated in protection from HIV in several vaccine trials but their action was poorly understood.

“These results show what a slippery customer the HIV virus is, but also shows that these ADCC antibodies are really forcing the virus into changing, in ways that cause it to be weaker,” he said.

“It also implies that if good ADCC antibodies were available prior to infection, via a vaccine, we might be able to stop the virus taking hold. This is the holy grail.”

The group at the University of Melbourne’s Department of Microbiology and Immunology analysed blood samples of people with HIV and found their virus had evolved to evade or ‘escape’ the ADCC antibodies their bodies are making to try to control their virus.

The team led by Dr Ivan Stratov and Professor Kent employed a novel technology developed in their laboratory to find where ADCC antibodies were attacking the virus. They then looked at how the sequence of the virus had mutated over time to avoid the immune response.

“There is an urgent need to identify effective immunity to HIV and our studies suggest ADCC responses apply significant immune pressure on the virus,” Dr Ivan Stratov, a clinician and researcher said.

There are more than 33 million people living with HIV worldwide, with nearly 30,000 in Australia. In 2009, around 370,000 children globally were born with HIV, bringing the total number of children under 15 living with HIV to 2.5 million.

HIV damages the immune system, with the body becoming vulnerable to ‘opportunistic infections’ (originally known as Acquired Immunodeficiency Syndrome, or AIDS). These infections are called ‘opportunistic’ because the weakened immune system gives them the ‘opportunity’ to take hold. The infections can cause death.

AIDS was first diagnosed in 1981. Since then HIV and AIDS have spread rapidly and cases have been reported in more than 150 countries.

“Creating an effective vaccine to HIV is critical for improving global health and reducing the further spread of the AIDS virus. We are excited to have come this far, with more advances expected in the next few years,” Dr Stratov said.

The group is now working on designing HIV vaccines to induce ADCC antibodies that are more difficult for the virus to escape.

Levinia Crooks, Chief Executive Officer of the Australasian Society for HIV Medicine, said the research discovery was promising. “It offers hope that one day there may be a vaccine against this terrible disease and reduce the number of people suffering as a consequence of being afflicted with HIV.”

Dr Stratov said blood samples kindly donated from people with HIV were instrumental in enabling their research. “We are very grateful to them for providing these samples to us, to enable us to try and make a real difference in both treating and preventing HIV.”

The work was published in the prestigious international journal PNAS.

See: www.microbiol.unimelb.edu.au/people/kent/allprojects.html#adcc