By David N. Leff

Lyme disease soon will be raising its seasonal head again on the East Coast of the U.S., including the woodsy North Shore of Long Island, New York.

Amid this happy hunting ground for the deer tick (Ixodes dammini) and its bacterial passenger, Borrelia burgdorferi, rise the buildings of the Brookhaven National Laboratory. There, in the biology department, protein crystallographer Catherine Lawson has just announced the crystal structure for a likely Lyme disease antigen, outer surface protein A (OspA). Her paper appears in the current Proceedings of the National Academy of Sciences, dated April 15, 1997.

"That structure," Lawson told BioWorld Today, "is completely different from crystals of other proteins. Nothing has been seen that's like it at all. We're not completely sure what to make of it immunologically," she added, "but we think that the two beta-sheet strands that form the immunologically interesting unit may have the ability to vary quite a bit, just because of the way they're structured on the protein."

That moving target, Lawson pointed out, is not like the antigenic evasion practiced by other pathogenic parasites. "As far as we could understand," she said, "the different strains of the Borrelia spirochete don't really change their coat. It's not like trypanosomes in sleeping sickness or Borrelia hermesii in relapsing fever, where you see things change every week, or a different mutated surface protein. That doesn't go on in B. burgdorferi."

What does go on is that the Lyme disease bacterium exists in several strains out in the field. "It's perhaps lucky," Lawson observed, "that on the East Coast it's predominantly a couple of different strains that are very closely related. So in principle, a good vaccine for everybody on the East Coast could be designed with just one or two different variants of the protein."

Strangely, she recalled, "Patients hardly ever had antibody responses to the OspA antigen, so that was a big mystery for a long time."

Then, in 1995, scientists at the Rocky Mountain Laboratory, in Hamilton, Montana, "figured out," Lawson said, "that this spirochete actually does change its coat * but just once. The tick is expressing this protein on its surface," she explained, "but when the blood meal begins, the spirochete divides and begins expressing OspC, a completely different protein. We're working on its structure too.

"By the time the tick gets into its mammalian host, human or mouse or deer, it's no longer expressing OspA any more. So you have to have a good titer of OspA antibodies in your bloodstream when the tick is biting, in order to prevent the bacteria from growing. So probably the future is going to be multi-component vaccines." (See BioWorld Today, June 24, 1996, p. 1.) *