Exclusive condominium seeks assistant for gullible security guard. Candidate should be equipped to spot troublemakers and turn them away. Duties include knowing when to call for  back-up to help keep out riffraff and poseurs.

If the brain housed an exclusive condominium, the facility would likely be in the market for a new security guard.

A recent study led by St. Jude Children’s Research Hospital scientists found that a cell surface molecule the brain relies on to act like a security guard—turning away bacteria and other threats—is easily duped.

That molecule is the laminin receptor (LR). Instead of protecting the brain by helping cells maintain a tight seal around it, the LR may be tricked by infectious agents. When the LR opens the door and provides a path into the brain, these agents make themselves at home, often with devastating results.

Enter Elaine Tuomanen, MD, St. Jude Infectious Diseases chair. She and her colleagues recently discovered that the LR plays a pivotal role in nearly all cases of bacterial meningitis. When trying to infect the brain, other agents, including viruses, prions and poisons secreted by the E.colibacteria, also target the LR.

In search of sidekicks

Tuomanen’s group wants to give LR some help, possibly sidekicks better equipped to spot troublemakers and turn them away. In this case, the sidekick might be a vaccine to spark production of an immune system component known as an antibody. Antibodies are part of the body’s front-line defense against disease.

“If you can block the door, you will block a lot of disease-causing organisms of the brain,” Tuomanen explains. She and her team have detailed LR’s role in allowing three bacteria responsible for nearly all bacterial meningitis to infiltrate the brain.

Bacterial meningitis is an inflammation of the membrane covering the brain and spinal cord. Once bacteria enter the cerebrospinal fluid bathing the brain and spine, they multiply rapidly. The resulting inflammation kills 30 percent of patients and leaves some survivors with devastating brain damage.

Tuomanen has devoted her professional life to combating one of the leading causes of bacterial meningitis, a bug known as Streptococcus pneumoniae. The microorganism enters the body through the nose. From there, pneumococcus sometimes moves on to infect the lungs, blood and brain, leaving pneumonia, ear infections, other illnesses and even death in its wake. Although vaccines are available against the most common types of the pneumococcus, the bacterium still kills as many as 1 million individuals every year, mostly young children living in developing countries.

Interviewing candidates

Along with deciphering how pneumococcus and other bacteria invade the brain, Tuomanen guides St. Jude involvement in an international coalition working to develop a safe, affordable, protein-based vaccine effective against all of the 90-plus strains of pneumococcus. Known as the Pneumococcus Vaccine Consortium, the group began work in earnest in 2007 and has attracted leading scientists from industry, academic and research centers plus support from PATH, an international nonprofit group based in Washington D.C. PATH is short for Program for Appropriate Technology in Health.

The cooperative effort has already generated more than a dozen potential vaccines now being tested in laboratory models. Within a year, the most promising will likely be ready for human trials.

St. Jude scientists have not only supplied vaccine candidates, but also made all the consortium’s experimental vaccines. That work was done in the hospital’s Protein Production Facility. Available to all St. Jude faculty, this facility is designed to help speed translation of scientific discoveries into better medical care.

As the consortium’s work moves to human trials, those experimental vaccines will be made in the Children’s GMP, LLC. The Good Manufacturing Practices (GMP) facility operates under government-approved manufacturing guidelines and produces the highly specialized medicines and vaccines that pharmaceutical companies are reluctant to pursue.

“To have the Protein Production Facility and the GMP facility on campus makes St. Jude unique in the world of medical science,” Tuomanen says. “There is no one out there who will make new vaccines for children. It is too hard and too expensive. We are in a position to make this difference. No one else has this capability. It is a perfect match to the St. Jude mission.”

Even as researchers push ahead with efforts to produce a universal pneumococcal vaccine, Tuomanen sees an exciting opportunity to broaden vaccine protection against bacterial meningitis by studying LR. Tuomanen and her colleagues recently found that the three bacteria responsible for nearly all bacterial meningitis begin their assault on the brain at LR. Pneumococcus, Neisseria meningitidesand Haemophilusinfluenza use different proteins to adhere to LR. But once they do, researchers report a biochemical cascade begins. The end result is meningitis.

“The findings suggest there is a common way to stop the bacteria responsible for the most common forms of meningitis,” Tuomanen explained. LR is a good place to start.

Reprinted from Promise, Autumn 2009

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