http://www.nytimes.com/2001/02/20/health/20LYME.html

 

February 20, 2001

 

Findings Boost Hope for Better Lyme Vaccine

By HOLCOMB B. NOBLE

Like a villain traveling incognito, the elusive germ that causes Lyme disease can disguise itself and evade vaccines by changing the chemistry of its outer coat with surprising complexity, scientists have found. This chemical virtuosity, they say, helps explain why the current Lyme vaccine has not been more protective.

Dr. Aravinda M. de Silva, a microbiologist at the University of North Carolina School of Medicine and the chief author of a new study, said the findings should provide important clues for developing a more effective vaccine. The study shows that in fighting Lyme bacteria, or Borrelia burgdorferi, “things are a lot more complicated,” Dr. de Silva said in an interview.

Lyme disease is usually transmitted through the bite of deer ticks, which carry the bacteria. It had previously been believed that basically two important proteins are produced on the bacteria’s outer surface and that one is eventually replaced by the other. Outer surface protein A (OspA, pronounced osp-ay) resides in the stomach of the deer tick before it bites human or animal to feed itself.

It was thought that the other, OspC, replaced the first, after the bite, when the bacteria made its way into the bloodstream of its new host. The current Lyme vaccine was designed to destroy OspA and therefore kill the bacteria.

“To our surprise, what we observed was not simply a matter of one protein being expressed in the gut and another in the host,” Dr. de Silva said. “What the tick actually spits into the host is a bacteria population that is highly variable.”

The study, whose co-authors were Dr. Jun Ohnishi, a postdoctoral researcher, and Dr. Joseph Piesman, of the division of vector- borne diseases at the Centers for Disease Control and Prevention in Atlanta, was reported last month in The Proceedings of the National Academy of Science.

Dr. Mark Hanson, director of molecular microbiology for MedImmune of Gaithersburg, Md., which has developed a vaccine candidate it has licensed to a major drug maker, called it a “big advance” in understanding how a Lyme vaccine has to work.

Dr. de Silva’s team injected female mice with the Lyme bacteria, which are part of the class of spirochetes, already known as “the great impostors” for their ability to avoid detection and cause illnesses that masquerade as a wide variety of other disorders like multiple sclerosis or lupus. This often makes it difficult to diagnose, as well as vaccinate against.

Two to three weeks later the mice were tested for Lyme disease, and were found to have been infected and carrying not one but four types of outer surface protein, one of which was encoded by a gene called vlsE that may produce many more, the scientists said.

The current Lyme vaccine, called Lymerix, manufactured by the pharmaceutical giant GlaxoSmithKline, targets only one of those proteins, OspA. The vaccine, made of genetically engineered OspA, causes creation of antibodies from the body’s immune system to attack that protein. When the tick bites a vaccinated human to suck blood, it also ingests antibodies, which reach the stomach of the tick and when all goes well kill the spirochete before it enters the human. In clinical trials of the vaccine in 1995 and 1996, nearly 11,000 people were studied and the vaccine was found 75 to 80 percent effective after the first year, but researchers have begun to question how long the protection lasts.

“It was a decent vaccine as far as it went, but its effect does not appear to last very long,” Dr. de Silva said, adding that one reason might be that the antibodies must travel into the tick instead of operating as they normally do inside the human or animal that is infected. The principal location of the OspA protein was not known when the clinical trials of the OspA vaccine began. GlaxoSmithKline said it had applied to the Food and Drug Administration for permission to give a second-year booster.

“It was pure chance that the vaccine happened to work in the tick the way it did,” Dr. de Silva said. “If people had known that the OspA was mainly produced within the unfed tick, they probably wouldn’t have tried to develop this vaccine.”

If the spirochete is not killed inside the tick and makes its way into the bloodstream of the person bitten, the germ changes into several of the other forms that can evade the vaccine’s defenses and continue to multiply and cause harm, he said. The OspA vaccine was developed and patented by three scientists at Yale; they did not respond to repeated phone calls for comment.

The trick, the North Carolina researchers said, is to find a “magic bullet,” or in this case, a magic target for making a new vaccine.  What is needed, they said, is to find some common chemical element — some protein that exists in all life cycles of all Lyme spirochetes.  Then researchers can try to design a vaccine that will specifically attack that element.

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.