CHAVI Announces International Search for HIV-Response Genes
by Becky Oskin

A pioneering collaboration among U.S., European and Australian researchers will seek to identify genetic differences in the way people respond to HIV. Through the new partnership, led by Duke researchers, investigators who once competed to unravel the mysteries of HIV will share access to patient groups they have studied.

Support for the collaboration is provided by the Center for HIV-AIDS Vaccine Immunology (CHAVI), a consortium of universities and academic medical centers established last year by the National Institute of Allergy and Infectious Diseases (NIAID) and directed by Barton Haynes, M.D., professor of medicine and director of the Human Vaccine Institute at Duke. CHAVI's initial mission is to find out what the immune system does during HIV infection particularly in the rare individuals who control the infection in their own way and try to produce a vaccine to mimic those responses.

“We intend to use natural genetic differences among people to point the way toward the most promising avenues for vaccine development,” says David Goldstein, Ph.D., director of the Center for Population Genomics and Pharmacogenetics at the Duke Institute for Genome Sciences & Policy and director of CHAVI's host genetics research core. “We want to find out why some people naturally hold the virus down to almost undetectable levels while others lose control of it quickly.”

The newly organized group, called EuroCHAVI, will recruit 600 patients from Switzerland, Spain, Denmark, Italy, Germany, the United Kingdom and Australia. EuroCHAVI aims to quickly identify common genes wherever they are in the human genome that affect how the body responds to HIV. “Because of the willingness of researchers throughout the world to work together, the prospects are very real for getting answers by next year,” Goldstein says.

Despite repeated exposures, some people apparently never become infected with HIV. Among those who become infected, there is dramatic variation in how the body responds to HIV and in how long it takes for infection to progress to AIDS. EuroCHAVI scientists will try to understand these differences by searching for an underlying genetic influence.

CHAVI is a consortium of scientists from Duke, Harvard University, the University of Alabama at Birmingham, the University of North Carolina at Chapel Hill and Oxford University in the United Kingdom. The grant from NIAID to establish and support CHAVI could total as much as $300 million over seven years.

For more information about CHAVI, visit http://chavi.org.

Gene Interaction Raises Autism Risk in Blacks, Whites
by Becky Levine

A combination of two malfunctioning genes increases the risk of autism among African Americans, according to a new study by Duke researchers. The team reported last year that this same gene combination also increases the risk of autism in Caucasians.

The finding will be critical to developing new treatments for both African Americans and Caucasians, the researchers say. They believe their new study is the first to examine the genetics of autism in African Americans, despite the disorder's equal prevalence across ethnic groups. Up to 1.5 million people in the United States have autism, the nation's fastest growing developmental disability

“It is essential that we define which genes play a role in particular ethnic groups so we can devise treatments that target the specific malfunctioning genes,” says Margaret Pericak-Vance, Ph.D., director of the Duke Center for Human Genetics and senior author of the study.

Duke members of the research team include Ann L. Collins, Ph.D., Deqiong Ma, M.D., Ph.D., Patrice L. Whitehead, Eden R. Martin, Ph.D., Michael L. Cuccaro, Ph.D., and John R. Gilbert, Ph.D. The research has been published in the online version of Neurogenetics and in the July 2006 print edition of the journal.

In their study, the Duke researchers searched along chromosome 15, which had previously been linked to autism, for genes that regulate a brain chemical (neurotransmitter) called GABA. GABA inhibits nerve cells from firing once their message has been transmitted. In this way, the neurotransmitter acts as an information filter that prevents the brain from becoming overstimulated.

If the GABA system malfunctions, the brain can be flooded with sensory information that overwhelms the brain's processing capabilities, leading to some of the behaviors that characterize autism. In African Americans and Caucasians, the interaction of two malfunctioning GABA receptor genes can increase the risk of autism.

Identifying relevant genes has been difficult precisely because multiple genes must interact to confer risk, Pericak-Vance says. In fact, scientists hypothesize that as many as 100 genes may be involved in autism.

Duke Testing New Flu Vaccine
by Becky Oskin

Duke is participating in a multicenter clinical trial to test the immune responses to an influenza vaccine manufactured in Australia. The trial, sponsored by the National Institute of Allergy and Infectious Diseases, is evaluating vaccine produced by CSL Limited, a company that has been manufacturing flu vaccine for nearly 40 years.

In 2004, nearly half of the normal supply of seasonal influenza vaccine in the United States was unavailable when one of two manufacturers of FDA-licensed flu vaccine had to withdraw its product due to safety concerns. This event highlighted the need for a greater number of manufacturers to make their influenza vaccine available in the United States.

“We need to ensure more secure supplies of influenza vaccine,” says Emmanuel Walter, M.D., associate director of the Duke Clinical Research Institute's Primary Care Research Consortium and leader of the Duke study.

Trial participants will receive varying strengths of the vaccine. Volunteers will be randomly assigned to different groups, either receiving one of four formulations of the vaccine or a placebo. As with current flu vaccines given yearly in the U.S., the Australian vaccine causes the body's immune system to make antibodies to fight infection, Walter says.

The study will examine an inactivated flu virus vaccine, made the same way as existing vaccines. "There is no live flu virus in the vaccine, and there is no risk of volunteers contracting flu or spreading it to others," Walter says. More than 40 million doses of the Australian-manufactured vaccine have been administered, and reported side effects are very similar to other flu vaccines.

If interested in participating in the study, call 919-620-5354.

Older Blood Associated with Worse Outcomes after Heart Surgery
by Richard Merritt

Older stored blood transfused into patients undergoing repeat heart surgery is associated with a significant increased risk of death, both during a patient's hospital stay and over the longer term following discharge, according to a new analysis of 321 patients by researchers from Duke and Columbia University.

Use of older blood also is associated with an increased risk for kidney problems, acute respiratory distress, and longer confinement to intensive care units.

“Scientists have long known that red blood cells undergo significant changes during their storage, but little had been known about whether or not these changes have any clinical implications for patients,” says Elliott Bennett-Guerrero, M.D., an associate professor of anesthesiology at Duke and lead investigator. “We believe our findings provide intriguing avenues for future study.”

The paper appeared in the June 22 issue of the journal Anesthesia & Analgesia. The other Duke member of the team was Mark Stafford-Smith, M.D., associate professor of anesthesiology.

The researchers examined the records of patients who had undergone a repeat open-heart procedure, hypothesizing that the effect of storage would be more pronounced in a population more likely to receive multiple blood transfusions. Patients in the study received an average of five units.

National blood banks require that blood can be stored for only 42 days after donation. After that time, unused blood must be discarded.

The study was not designed to uncover the actual physiological mechanisms that cause the observed health problems, Bennett-Guerrero says. But previous reports have hinted at a number of possibilities. For example, transfused blood loses oxygen-carrying ability over time and may stimulate an immune response in its recipient. In addition, red blood cells become stiffer over time, which could affect their ability to fit into or move through capillaries and deliver oxygen, he adds.