SIGHTINGS


 
New AIDS "Vaccine"
Candidate May Cause AIDS
By Daniel Q. Haney
The Associated Press
7-4-98
 
 
GENEVA -- A weakened virus that many consider the best hope for an AIDS vaccine suffered a serious setback Thursday when tests in adult monkeys showed it may actually cause the disease it was meant to prevent.
 
The approach -- what scientists call a live, attenuated vaccine -- initially protects monkeys from getting infected with the simian version of HIV.
 
However, the new work shows that over time, the weakened virus can mutate into a lethal form that causes the disease it was meant to prevent.
 
"To me, this fortifies that we are not ready to go into humans with a live attenuated vaccine," said Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases.
 
Dr. Robert Gallo of the University of Maryland said that if the live attenuated approach fails, it means AIDS vaccine development is no further ahead than it was in 1984, when little was known about the epidemic's cause.
 
"We have no guarantee that we will ever have a vaccine," he said.
 
Creating an AIDS vaccine is a top priority of researchers but also an extraordinarily difficult task because the AIDS virus attacks parts of the immune system that are ordinarily called into action by effective vaccines.
 
One idea is to give people a weakened version of HIV -- one that would set up a harmless low-grade infection but keep immune defenses on high alert against the real thing. People who carry genetically crippled HIV that arose through random mutations do not seem to get sick.
 
Because of the obvious hazards of testing even a weakened AIDS virus on people, scientists at the New England Regional Primate Center in Southboro, Mass., created a mirror version using the closely related simian immune deficiency virus, SIV.
 
When first tested on macaque monkeys, they found that the vaccine seemed to completely protect them from what should have been lethal doses of the full-strength virus.
 
However, in 1995, Dr. Ruth Ruprecht of Dana Farber Cancer Institute in Boston found that the weakened virus eventually triggered the simian version of AIDS when given to baby monkeys.
 
At the 12th World AIDS Conference, Ruprecht reported her new research shows that in time, the vaccine also causes AIDS in adult monkeys.
 
"What we saw in infants is a fast-forward version of what could happen in adults with an attenuated vaccine," she said.
 
The version of the vaccine she tested was weakened by deleting parts of three genes that were thought necessary for it to cause illness.
 
Los Angeles AIDS specialist Charles Farthing, who wants to test a live attenuated HIV vaccine in people, called Ruprecht's latest discovery "more concerning" than her earlier work in infants. Still, he said, monkey AIDS is an even more virulent disease than human AIDS, and the human vaccine would be weakened even more than the monkey version she tested.
 
"Looking at SIV in monkeys gives you a misleading impression of what would happen in human beings," he said. "This is not safety data for humans."
 
Ruprecht vaccinated 15 adult monkeys over the past three to five years. One has died of AIDS. Three others have high levels of the HIV virus in their blood.
 
Among nine infant monkeys vaccinated, six have developed AIDS and five of them are dead. The other three have pre-AIDS abnormalities.
 
She said the weakened virus mutates so rapidly that strains eventually emerge that are able to thrive.
 
"There is a mini-Darwinian experiment going on in every single vaccinated animal," she said. "In the end, we have disease."



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