June 6, 2008

Grant takes HIV research in new direction

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James Crowe, M.D., left, and Mark Hicar, M.D., Ph.D., are studying new avenues of HIV vaccine research. (photo by Neil Brake)

Grant takes HIV research in new direction

After recent efforts to develop a vaccine to protect against AIDS proved ineffective, the National Institutes of Health announced a change in research direction; and it's one that will involve the lab of James Crowe, M.D., professor of Pediatrics, Microbiology and Immunology at the Monroe Carell Jr. Children's Hospital at Vanderbilt.

Crowe is one of 10 principal investigators across the nation receiving support from a newly announced, $15.6 million, five-year push to strengthen and expand knowledge of B cells. Crowe's lab will receive $2.4 million over five years for a study currently entitled “Clonal Analysis of the Human B Cell Response to HIV.”

“Researchers in HIV vaccine work have long thought T cells were the key to HIV immunity, and all recent vaccines were designed to stimulate T cells, but the last major Phase 3 trial of an HIV vaccine in humans showed simply inducing T cell immunity doesn't work.” Crowe said.

While research into T cells continues, funding has been scaled back in that area while the government stimulated growth in the area of B cells. The change is an exciting development for the Crowe lab.

“Our lab has developed very powerful tools for the study of human B cells, the body's source of antibodies,” Crowe said. “We can take blood from an immune individual and find rare, one-in-a-million cells with antibodies of interest, and we can pull that needle out of the haystack.”

His lab has been developing and using these techniques with B cells to create monoclonal antibodies as well as describe the cells' role in the body's defense against rotavirus and respiratory syncytial virus (RSV) in children.

“It's an honor for one of our investigators to be included in this elite research group,” said Jeff Balser, M.D., Ph.D., associate vice chancellor for Research and interim dean of the School of Medicine. “Jim Crowe is a highly innovative scientist, and it's no surprise that he's part of this new program to study B cells in neutralizing HIV.”

This National Institute of Allergy and Infectious Diseases grant will fund research to isolate human monoclonal antibodies to HIV, and to study HIV-specific human B cell “repertoires” in a very special adult population, one that has been cultivated by Spyros Kalams, M.D., director of viral immunology studies in the Vanderbilt Infectious Diseases Unit.

These subjects are sometimes called controllers, meaning people who either manage to keep the HIV viral load very low, or who have lived with HIV for a decade or more without developing AIDS.

“We may be able to learn how the antibodies of these subjects kill the viruses with which they are infected,” Crowe said. “If we can learn what the targets are on the virus that are most vulnerable to the killing action of antibodies, we might be able to design a vaccine antigen that could protect people who are not infected.”

The hope is that a B cell vaccine may allow for a more effective response to HIV than T cell vaccines were able to induce. The goal Crowe ultimately would like to achieve is stimulating antibodies that have unique powers to broadly neutralize HIV and its many mutations.

Crowe's initial goal is to show how HIV controllers' B cells do what they do, and if he can show that antibodies can be produced, the next step would be testing a new line of vaccines based on the features of HIV discovered using B cell technology.