New OMRF finding could help improve vaccines

OKLAHOMA CITY, September 8, 2009 – As a resurgent H1N1 flu virus worries medical professionals and families, more people are looking to vaccines to keep them safe. Now a new discovery by scientists at the Oklahoma Medical Research Foundation could shed light on why vaccines are ineffective in some patients.

In a paper published in the current issue of the Journal of Biological Chemistry, OMRF researchers Shikha Malhotra, Ph.D., Susan Kovats, Ph.D., and Mark Coggeshall, Ph.D., describe for the first time a crucial part of the process—when immune cells take in the vaccine.

Vaccines work by introducing a weakened or dead virus into the immune system. Then B cells, white blood cells that play a central role in the body’s immune response, create antibodies that stand ready to fight any more potent version of the virus that might later attempt to enter the body.

To create antibodies, the B cell absorbs the protein from the vaccine and “presents” the plans for antibodies to an intermediary—known as a T helper cell. The T helper cell then tells the cell whether or not it should create the illness-fighting antibodies.

“On the surface, it seems oddly inefficient,” said Coggeshall, who holds the Robert S. Kerr Jr. Endowed Chair in Cancer Research at OMRF. “Why not just have the cell start making antibodies?”

But according to Coggeshall, the T helper’s role is crucial. “That extra step is for safety. It helps keep our immune system from creating rogue antibodies that could hurt us.”

Understanding how B cells draw in vaccines could help us understand why some people fail to respond to vaccines. Work done by OMRF’s Judith James, M.D., Ph.D., finds that more than half the soldiers vaccinated with anthrax do not make enough antibodies.

“Virtually nothing is known about this process we’ve identified,” Coggeshall said. “We need to know how it works correctly so we can start figuring out why it sometimes goes wrong.”

Going forward, the OMRF researchers will study reactions to vaccines and see if those who react poorly are missing the right proteins for immune cells to accept the vaccine. “We will start to apply this work to flu and anthrax vaccine recipients,” said Coggeshall.

By learning more about how vaccines signal the immune system, scientists may be able to predict which vaccines will prevent influenza and other viruses. This research could also prove crucial in developing treatments to help patients who might not react properly to vaccines.

“Lots of people don’t react or have a substandard reaction to vaccines,” said Coggeshall. “It might be that those people lack the machinery in their B cells to pull in the vaccine. That’s what we want to study next.”

OMRF is an independent, nonprofit biomedical research institute dedicated to understanding and developing more effective treatments for human diseases. Chartered in 1946, its scientists focus on such critical research areas as Alzheimer’s disease, cancer, lupus and cardiovascular disease.

Scientists at Duke University also participated in this research project.

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