APRIL 14, 1997


UPTON, NY -- Tantalizing clues in the mystery of Lyme disease have been uncovered at the U.S. Department of Energy's Brookhaven National Laboratory.

Scientists from BNL and the School of Medicine at the State University of New York (SUNY) at Stony Brook have built the first detailed atomic model of an important Lyme disease protein, called OspA, that is already being tested in humans as an experimental vaccine. (structure shown above)

The structure, which is being published in the April 15 issue of the Proceedings of the National Academy of Sciences, will aid vaccine developers in designing improved second-generation vaccines more effective in blocking the disease's transmission. Lyme disease strikes more than 10,000 Americans each year, through a bacterial infection that causes rashes, fever, arthritis and even nerve damage.

"OspA is an important piece in the Lyme disease puzzle," said Brookhaven biophysicist and co-author Cathy Lawson. "And we now have a firm foundation for the identification of the regions of the protein that interact with the body's immune system in the vaccine to help the body ward off future infection."

Dr. Lawson and her colleagues studied the protein using intense X-rays at BNL's National Synchrotron Light Source facility. Their results are being made available to the scientific and pharmaceutical community through the Protein Data Bank, based at BNL.

A Key Lyme Protein

Lyme disease was named for a town in Connecticut where a cluster of arthritic children and adults led to the discovery of the bacteria, called Borrelia burgdorferi, that caused their symptoms.
Now an increasing health concern in the northeastern U.S, Lyme disease infects mice and deer and is transmitted to humans via the bite of tiny blood-feeding deer ticks. Although treatable with antibiotics, Lyme disease can be hard to diagnose, and untreated infections can progress to severe complications. As a result, there has been a growing desire for a safe, effective vaccine to prevent the spread of infection.

Scientists know that before a tick bites a victim and begins its "bloodmeal", Lyme bacteria lingering in the tick's midgut display OspA on their cell surfaces. Studies have already shown that laboratory animals vaccinated with OspA do not develop Lyme disease they become immune to the transmission of the bacteria from a tick bite.

But vaccination can fail if the bacteria in the tick are of a different strain than the bacteria used to make the vaccine the slightest difference in the protein's structure is all it takes. The BNL-Stony Brook structural model of OspA shows the exact locations where different strains of Borrelia vary. That will make it useful in the development of vaccines that protect against many strains. Results are expected soon from trials being conducted by two pharmaceutical companies to see how effective first-generation OspA vaccines are in preventing Lyme disease in humans.

Mighty X-Rays

To make the structural model of OspA, Lawson and her colleagues first needed to make crystals of the protein that could withstand intense X-rays. They used the T7 gene-expression system developed at BNL to make large quantities of OspA.

When attempts to crystallize the protein failed, Stony Brook collaborators provided an antibody derived from a mouse that had been infected with the Lyme bacteria. That antibody, which specifically recognizes OspA, was divided into smaller pieces called Fab fragments. Mixing OspA with the Fab formed a complex that could be crystallized and X-rayed.

Then, the researchers brought the crystals to Brookhaven's National Synchrotron Light Source. There, they fired strong beams of X-rays at the crystals and recorded how the rays diffracted through them. Using powerful computers, they turned the diffraction patterns into the three-dimensional map that led them to the atomic models of the OspA and the Fab.

BNL and Stony Brook are appropriate locations for Lyme disease research not only because of their advanced scientific facilities but also because of Long Island's high rates of the disease. Other Lyme-related work at both institutions includes studies of diagnosis and treatment techniques, immune response, protein expression and genome sequencing.

BNL and Stony Brook have been collaborating on Lyme research for over five years, with funding from the National Institutes of Health and the Department of Energy.

Brookhaven National Laboratory carries out basic and applied research in the physical, biomedical and environmental sciences and in selected energy technologies. BNL is operated by Associated Universities, Inc., a nonprofit research management organization, under contract with the U.S. Department of Energy.

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