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Study shows how some AIDS vaccines may harm
  Thu Nov 15, 2007 5:55pm EST
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - Some viruses being used in experimental AIDS vaccines may damage the immune system by exhausting key cells, researchers reported on Thursday in a finding that may further cloud the field of HIV vaccines.
They said vaccines using the viruses should not be tested on people until more studies are done. But other vaccine experts said the findings, while scientifically interesting, were not a cause for immediate alarm.
The usually harmless viruses are used as so-called vectors to carry genetic material from the AIDS virus into the body so that the immune system can recognize and rally against it.
But the viruses, called adeno-associated viruses, may themselves be doing harm, said Dr. Hildegund Ertl, director of the Wistar Institute Vaccine Center in Philadelphia.
In mice, the adeno-associated virus, or AAV vaccines, directly interfered with immune cells called CD8 T-cells, Ertl's team reported in the Journal of Clinical Investigation. These are the "killer" T-cells that a vaccine is supposed to muster to fight HIV.
"The immune cells become exhausted," Ertl said in a telephone interview.
"It is simply a defense mechanism of T-cells -- if there is too much antigen for too long a time they simply turn themselves off."
Antigens are the proteins the immune system uses to recognize enemies such as bacteria and viruses. In the case of HIV, turned-off T-cells could leave a person more vulnerable than usual to infection.
"AAVs do not cause disease," Ertl's team wrote. They cannot even replicate on their own, instead piggybacking onto adenoviruses, which cause colds, or herpes viruses.
But they do persist in the body.
Ertl said it was unclear whether her findings might cast light on the troubling developments in a trial of an AIDS vaccine that used another virus, an adenovirus.
Vaccine maker Merck & Co stopped that trial in September and said last week it appeared that the adenovirus used in the vaccine may have somehow made patients more vulnerable to HIV infections.
The International AIDS Vaccine Initiative or IAVI used an adeno-associated virus in a trial of an AIDS vaccine that wrapped up in January in Belgium, Germany and India, and another in South Africa, Uganda and Zambia.
IAVI's Pat Fast said the group was not testing AAV vaccines any more.
"While we find the AAV study by Dr. Ertl and her group ... very interesting and we'll consider whether it can inform our future studies, their study was conducted in mice and there are fundamental differences between mice and humans in their respective immune responses, particularly with regard to the immune response against HIV," Fast said in a statement.
"The dose given to these mice was equivalent, on the basis of body weight, to 3,000 to 4,000 times the highest dose given to humans in the ... study in India."
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the study should be taken "with a very heavy dose of caution".
He noted that adenoviruses and adeno-associated viruses are very different microbes, despite the similarity of their names.
"We may be dealing with apples and oranges," Fauci said in a telephone interview.
(Editing by Mohammad Zargham)
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