The Telegraph
Since 1st March, 1999
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Danger signal over HIV vaccine
- Study says injected virus can cripple the body’s immune system

New Delhi, Nov. 18: A virus used in experimental HIV vaccines given to volunteers in India, Europe and South Africa cripples the immune system in mice, a new study has revealed.

Scientists at The Wistar Institute in Philadelphia who conducted the study said their findings raised the possibility of vaccines that might do more harm than good.

Twenty-four people from Pune were among several dozen volunteers in India, Belgium, Germany and South Africa who had over the past two years received vaccines that used a genetically altered adeno-associated virus (AAV) to ferry HIV genes in the body to stimulate an immune response against HIV.

The AAV is believed to be a harmless virus, but the Wistar researchers have discovered that such vaccines impair immune system cells, called CD8 T, which play a key role in destroying HIV-infected cells.

The findings, published this week in The Journal of Clinical Investigation, show that while the AAV induced CD8 T cells, they couldn’t proliferate and weren’t very efficient at killing cells that mimic HIV-infected cells.

“The AAV vaccines against HIV may do more harm than good by robbing people of their natural immune response to HIV,” said Hildegund Ertl, who heads the immunology programme at The Wistar Institute, a 115-year-old biomedical research centre.

“If, after a vaccination, you have impaired CD8 T cells that cannot proliferate, you could be worse off than if you did not have the vaccine,” Ertl told The Telegraph in a telephone interview.

But other experts said the relevance of these findings to humans is unclear because they may be the effect of a high dose of the AAV given to the mice by the Wistar scientists.

“The dose given to these mice was equivalent to 3,000 to 4,000 times the highest dose given to humans in the study in India,” said Patricia Fast, medical affairs director of the New York-based International AIDS Vaccine Initiative, an agency leading a global effort to find a safe and effective HIV vaccine.

She said non-human primates are more like humans than mice, and there was evidence that macaques do mount a protective T-cell response after vaccination. “There is no evidence to suggest that the findings of impaired T-cell response are seen either in macaques or humans,” Fast said.

But the Wistar researchers believe that while their findings were based on mice, they were significant enough to warrant a fresh look at AAV vaccines. “Without additional pre-clinical (animal) studies, they should not be used in humans,” Ertl said.

The Indian and European trials of the AAV-based HIV vaccines — developed by a US company — concluded earlier this year. Officials of the AIDS vaccine initiative and scientists at Pune’s National AIDS Research Institute, who conducted the Indian arm of the trial, said the vaccine has had no serious side effects on any of the volunteers.

“These findings are a reminder of just how little we know about the human immune system,” said Satyajit Rath, a scientist at Delhi’s National Institute of Immunology.

The progression from HIV infection to AIDS hinges on a battle of numbers between CD8 T cells and HIV. When CD8 T cells can’t proliferate, the immune system loses its ability to check HIV in the body, and progress to AIDS could be faster.

Scientists at the AIDS research institute said the new findings were “unexpected”, but there were no reasons yet for concern about the volunteers.

“We gave the vaccine only to healthy volunteers who are not at risk of picking up HIV,” institute director Ramesh Paranjpe said.

He added that the health of each of the volunteers would be followed up for at least five years.

Dozens of candidate HIV vaccines have been tested on humans over the past two decades. Most have been safe, but stimulate immune systems weakly and haven’t advanced to efficacy trials.

The vaccine tested in Pune, Belgium and Germany generated an immune response in only 25 per cent of volunteers at the highest dose tested, scientists had reported earlier this year.

Part II Study triggers debate on whether scientists are rushing into human trials of experimental HIV vaccines without homework.

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