September 12, 2003

Graham: Teaching the immune system key to HIV vaccine

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Dr. Barney Graham speaks during the Vanderbilt-Meharry Center for AIDS Research Symposium Wednesday. Dana Johnson

Graham: Teaching the immune system key to HIV vaccine

The key to defeating HIV, one of the most wily viral foes known, may lie in teaching the body’s immune system to sweep away infected cells before they can spread the virus, Dr. Barney Graham, of the National Institutes of Health, said during a symposium at Vanderbilt on Wednesday.

Early vaccines against the human immunodeficiency virus, which causes AIDS, focused on an envelope protein, called gp120, that the virus uses to dock with its target cells in the immune system.

Scientists hoped that the protein itself could be an effective vaccine, triggering the production of antibodies that then would attack the virus as soon as it enters the body, and prevent infection. So far, results have been disappointing.

“There have been over 50 studies of more than 30 product concepts, and none has elicited the kind of antibody that we think can block infection and neutralize commonly transmitted strains of virus,” Graham, a former Vanderbilt AIDS vaccine researcher, said during the first Vanderbilt-Meharry Center for AIDS Research Symposium at the Vanderbilt University Club.

Current research is focusing on the CD8+ cell, a type of lymphocyte (white blood cell) that can clear its virus-infected neighbors from the bloodstream. Normally, this “sweep-up” operation occurs too late to prevent HIV from establishing itself in the body, so scientists are trying to find ways — through vaccines — to speed the operation up.

In animal studies and human safety and immunogenicity trials, modified synthetic genes that can make proteins similar in shapes and structures to viral proteins are being injected to produce these specialized cytolytic lymphocytes. This will be followed by a “booster shot” — a matching set of genes carried by a harmless adenovirus — to bolster the immune response.

The injected material cannot cause HIV infection, but in these early studies it has triggered strong responses as measured by a rise in both CD4+ and CD8+ cells, said Graham, who is chief of the Viral Pathogenesis Laboratory and Clinical Trials Core at the NIH Vaccine Research Center.

Combining a variety of HIV antigens into the vaccine has another advantage: It may help prevent the virus from sneaking around the body’s immune defenses, by changing its highly mutable envelope protein. That may improve the ability of the body to make antibodies that can recognize and prevent HIV infection, he said.

More studies, involving centers throughout the world, including Vanderbilt, are planned in coming months. Graham said he hoped the new product would be tested in a Phase III trial, which measures its ability to reduce or prevent infection in high-risk individuals, by 2005.

Controlling the AIDS epidemic, which is infecting 14,000 people throughout the world every day, will require more than a vaccine, however.

Graham said it also would require public health measures to prevent transmission, and extensive treatment with anti-retroviral drugs to reduce the viral “load” in the population.

Drug treatment not only can help control the disease in an individual, but epidemiological studies suggest it may reduce the likelihood that the individual will infect others, he said.