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November 2, 2009
Scientist on a conveyor belt of discovery

By Quinn Eastman

Most vaccines in use today are administered by injection. But scientists who study the immune system believe it may be better to deliver vaccines through the mouth or nose, thus strengthening the body’s defenses where the attack starts.

Ifor Williams, associate professor of pathology and laboratory medicine at Emory School of Medicine, thinks M cells, a type of cell found in the intestines, may be a key to effective mucosal vaccines. The results of Williams’ teams’ research were recently published by the Journal of Immunology.

For an orally delivered vaccine to stimulate the immune system properly, enough of it has to cross the barriers posed by mucosal surfaces, Williams says. Effective oral vaccines such as polio vaccine come from pathogens that preferentially stick to M cells and exploit them to invade mucosal tissues in the intestine.
M cells act like “conveyor belts” transporting small particles across the barriers and into Peyer’s patches, which resemble lymph nodes but are specialized for the intestines.

“As bacteria and food and other material come through the intestine, M cells divert a bit of that stream,” he says. “It’s how the immune system keeps track of what’s out there.”

Working with Williams, graduate student Kathryn Knoop discovered that a protein made by the body called RANKL (receptor activator of NF-κB ligand) is essential for the proper development of M cells.

Mice lacking the gene for RANKL have more than 50 times fewer M cells in their intestines, the authors found. The intestines in these mice also have trouble taking up fluorescent beads that are a stand-in for bacteria.

By injecting mice with artificial RANKL, the scientists could correct the defect. In addition, regular mice treated with RANKL had more M cells throughout their intestines. Usually M cells are found next to Peyer’s patches.

The Emory team has earned a Grand Challenges Explorations grant from the Bill and Melinda Gates Foundation to test their ideas. Williams says the Gates grant will allow his laboratory to test whether RANKL treatment can boost the immune response to oral vaccines in mice. Also, he plans to examine how RANKL treatment affects the mucosal surface inside the nose.

“We’re still trying to figure out if it works for other mucosal surfaces like those in the nose,” he says.

RANKL is also important for bone development and breast milk production. That means prolonged RANKL treatment throughout the body might have unwanted effects on bone density in humans, Williams says.
However, a temporary dose delivered through the nose could minimize those effects, and there may be more selective ways to stimulate development of M cells via the RANKL pathway, he says.

The current research was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation of America.