Emory Report
January 26, 2009
Volume 61, Number 17

Blocking immune protein in monkeys
In rhesus macaque monkeys severely infected with SIV (the nonhuman primate version of HIV), scientists blocked the PD-1 protein, which significantly reduced the plasma viral load and prolonged the monkeys’ survival. The therapy worked by boosting anti-viral killer cells (CD8 T cells) and improving antibody response.

“Our findings raise the possibility that PD-1 blocking antibody treatment not only could improve the anti-viral T cell response to chronic HIV infections, but it also could generate an effective antibody response against the mutated virus of the infected host,” says principal investigator Rama Amara, a Yerkes and Emory Vaccine Center scientist.

“This therapy was effective without anti-retroviral drugs and in monkeys with severe AIDS. It is critical to induce protective immune responses targeting the mutated virus for developing a successful immune therapy to control HIV infection.”

“These findings are important not only because they highlight a potential therapy for HIV, but also because of the insights they offer for other challenging chronic infectious diseases such as hepatitis C virus and tuberculosis,” says Vaccine Center Director Rafi Ahmed.
“Through the Grand Challenges in Global Health initiative, which also funded the current study, we soon will begin testing the PD-1 blockade against HCV in nonhuman primates.”

The research was published in Nature in December.



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January 26
, 2009
$13M joint effort for promising AIDS treatment

By Holly Korschun

A grant in support of AIDS research from parents who in 1989 realized that all children are at risk for contracting the disease has paved the way for a much larger NIH grant that could lead to promising new treatment targets.

Concerned Parents for AIDS Research, a New York-based group of parents, some of whom have lost children to AIDS, last year contributed $250,000 to the Emory Vaccine Center, led by Rafi Ahmed, a Georgia Research Alliance Eminent Scholar. The seed grant made it possible for Ahmed’s laboratory to collaborate with scientists at Harvard University on studies of a protein that inhibits the immune response to chronic infectious diseases like HIV.

Two years ago scientists at Emory and Harvard made the exciting discovery that the immune inhibitor protein PD-1 (Programmed Death-1) helps switch off the immune response to chronic infectious diseases. This results in apparent “exhaustion” of the T-cell response.

Because of the progress made through the initial seed grant, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) has awarded a $13 million, five-year program project grant that will allow the Emory scientists and their collaborators to focus on PD-1 and its specific role in HIV and other chronic viral infections. They plan to identify new targets and pathways and possible drugs that could aim for this molecular trigger, turn off the PD-1 protein, reactivate the immune response and possibly clear HIV infection.

“Emory put together amazing teams to leverage our private funding,” says Andrew Lipschitz, medical director of Concerned Parents for AIDS Research. He believes that future success in stopping AIDS depends on sharing ideas, sharing technology and sharing costs.

“CPFA’s goal was to bring together great scientists at two great universities,” he says. “Our initial grant made sense because Emory had certain techniques and equipment that Harvard did not and vice versa. Duplicating machinery and planning would have been very expensive. By sharing their ideas and technology, Emory and Harvard were able to increase their understanding of PD-1 and qualify for this NIH grant, which will enable collaboration with many other major institutions and help scientists move more quickly toward finding treatments and cures for HIV.”

With the NIH grant, the research team now includes scientists from Emory, Dana Farber Cancer Institute, Harvard Medical School, Massachusetts General Hospital, New York University, the University of Montreal and the University of Pennsylvania.

“It is now well established that T cell dysfunction is a cardinal feature of many chronic viral infections — most strikingly HIV, and also hepatitis C and hepatitis B. We have found that the PD-1 inhibitory pathway plays a critical role in this functional exhaustion of virus-specific T cells,” says project leader Ahmed.

“This collaborative grant, which includes an outstanding team of investigators, provides us a fantastic opportunity to investigate the unique properties of this PD-1 pathway that inhibits the immune response and impacts our defense against deadly infectious diseases. Our work also has clear implications for the treatment of tumors and autoimmune diseases and for increasing the success of transplantation, he says.”

The CPFA grant is part of the private support being sought for Campaign Emory, a $1.6 billion fundraising endeavor that combines private support and the University’s people, places and programs to make a powerful contribution to the world.