Danger signal over HIV vaccine trials in India ?

[Guest guest]

Danger signal over HIV vaccine: Study says injected virus can cripple

the body's immune system

G.S. MUDUR

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

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.

http://telegraphindia.com/1071119/asp/nation/story_8564688.asp