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February 17, 1998
MEDIA CONTACT: Marc Kusinitz
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Immune Response To HIV May Be Better Than Previously Thought

A Johns Hopkins study using genetically engineered cells strongly suggests that long-term survivors' immunity to HIV is more robust than previously thought.

One implication is that some experimental vaccines may be better than standard tests have shown, according to Stuart Ray, M.D., assistant professor in the division of infectious diseases. The results of the study, published in the Jan. 1 issue of AIDS and Human Retroviruses, also offer clues to why some infected with HIV live much longer than others. The work was supported in part by the National Institute of Allergy and Infectious Diseases.

The Hopkins scientists suspected that standard methods of measuring anti-HIV reaction by immune cells in the body were inadequate because the tests used laboratory strains of the AIDS virus rather than strains that actually infect people.

"Some proteins on the surface of lab strains of the virus differed from the natural strains," says Ray. "So there was the probability that results of standard tests wouldn't reflect accurately how well the immune system responds to an infection or to a vaccine. It made sense to test a person's immune response by using proteins from the same virus that he was infected with, rather than a laboratory strain."

Based on that hunch, the Hopkins scientists stimulated immune cells called CTLs taken from AIDS patients, using proteins from the same strain of HIV that infected them. CTLs are an important defense against HIV and attack the virus early in an infection, before anti-HIV antibodies appear, according to Ray.

To do this, the Hopkins team used genes from those viruses to genetically engineer a type of immune system cell called B cells, which were also taken from those patients. The B cells used the genes to make a type of HIV protein called Env, which is known to be an important target of the immune system. The scientists then stimulated the patients' CTLs by exposing them to the B cells carrying Env on their surfaces. The Env protein differs somewhat in different strains of HIV. Such mutations usually let the virus "hide" from anti-HIV antibodies made by the immune system. But the Hopkins researchers found that CTLs aren't so easily fooled.

"We found using this new test that people who are infected have a better immune response to HIV than previously thought," Ray says. "Different clones, or families, of CTLs from people infected with HIV become activated during an infection, and these clones can recognize a slightly different version of Env. These clones may recognize various strains of HIV even if they have not been previously exposed to them. That means the immune response to HIV is more robust than previously thought. And it means that the response to a vaccine carrying Env may be more robust as well."

Other authors of the study include Ndongala Lubaki, Bharati R. Dhruva, Robert F. Siliciano and Robert C. Bollinger.

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