MCG, UGA team up on research

A collaboration between Medical College of Georgia and the University of Georgia could have implications not only for pandemic flu and the novel influenza A H1N1 virus but for flu vaccine strategies in the future, the researchers said.

The partnership was awarded a 5-year, $2.9 million grant to study the implications of a chemical called indoleamine 2,3 dioxygenase, or IDO for short, and its potential role in muting immune response to influenza infection, possibly blunting vaccine response, and encouraging secondary infections such as pneumonia.

An MCG team lead by Drs. Andrew Mellor and David Munn caused a worldwide stir in 1998 when they outlined IDO's natural role in helping to protect a developing fetus, with foreign genetic material from the father, from attack by the mother's immune system. IDO has since been implicated in immune problems such as tumor survival, chronic infections such as HIV and autoimmune diseases.

The chemical might be one reason some vaccines fail to get an adequate immune response, said Dr. Mellor, director of the Immunotherapy Center and Georgia Research Alliance Eminent Scholar Chair in Immunogenetics at MCG.

"Vaccine strategies are full of failures," he said. "We think we've got another angle on this. We may be already in the best vaccines that are available, without knowing it, be avoiding the IDO mechanism. Maybe some of the ones that were really disappointments were actually, speculatively, IDO inducers which would make them not work very well."

Some of the things added to vaccines to boost them could actually be having an opposite effect by inducing IDO, Dr. Mellor said. That could have implications for creating vaccines for strains such as H5N1 avian flu, which has long been watched as a potential cause of pandemic flu, said Ralph A. Tripp, a professor of infectious disease and Georgia Research Alliance Eminent Scholar at UGA. That virus is a concern because it carries a mutation that allows it to cause a much more robust infection in the lungs than seasonal flu, he said. But vaccines from the strain need high doses to induce an adequate immune response, which could mean it needs some type of a boost. Dr. Tripp, who is also associate director of The Regional Center of Excellence for Influenza Research and Surveillance, one of six in the country, said the center's focus has been moved off H5N1 to work on the novel H1N1 virus currently circulating.

"We have the virus in the lab and we're working on it today," he said. What they learn about IDO could definitely be tied into that work later, he said.

"There's very good, strong overlap." Dr. Tripp said. "It's complementary and actually it is as cutting edge as it is going to get."

Earlier work by Dr. Mellor, published in 2006, pointed toward IDO's role in enhancing the progress of secondary infections from pneumonia.

"I kept saying that was an important observation some time ago but it fell on deaf ears," he said.

But now the collaboration aims to explore it. Pneumonia is a complication that is often the actual cause of deaths from influenza, Dr. Tripp said.

Ultimately, it might be the ability to look at all mechanisms to come up with better vaccines.

"That's what they are looking for, new approaches to vaccine development," Dr. Tripp said. "And this is the perfect time."