The Story of the Lyme Disease Vaccine

Scientists discovered the microbe that causes Lyme disease and contributed other insights that led to the production of a safe and effective vaccine for the prevention of Lyme disease. This achievement emphasizes the importance of basic research in providing knowledge to mount a timely response to emerging diseases.

Lyme Disease:  The Timeline of Its Discovery and the Development of a Vaccine 1975  First cases of Lyme disease reported. 1981  Microbe identified. 1989  The outer surface protein, OspA, found and cloned. Early 1990s  Antibodies to OspA found in many chronic Lyme disease patients. 1990-1992  Vaccinations with rOspA found to protect mice against Lyme disease infection. 1992-1995  Vaccinations with rOspA tested in other animals. 1995  Lyme vaccine found safe and effective in persons with Lyme disease. 1995-1998  Vaccine found safe and effective in people without Lyme disease. 1998  FDA approves Lyme vaccine. 2001  FDA withdraws Lyme vaccine from market.

More than 100,000 cases of Lyme disease have been reported in the United States, and the incidence is increasing each year. Approximately 12,500 new cases were diagnosed in 1997. Lyme disease can be difficult to diagnose because it is easily mistaken for other ailments, and existing laboratory tests can be inaccurate. Although Lyme disease can be treated successfully in the early stages with antibiotics, patients who go untreated or do not respond to antibiotics may develop significant complications months or years later. These problems may include painful arthritis, especially in the knees, nervous system difficulties, and heart complications. Treatment of early-stage Lyme disease alone costs an estimated $60 million a year in the United States.

Identification of an Emerging Disease

Lyme disease was first recognized in 1975, when researchers investigated several cases of arthritis among children living in Lyme, Connecticut. The researchers suspected that an unidentified infectious microbe caused the illness, because the sick children lived near each other and became ill at the same time. Many of the children also recalled being bitten by a tick before becoming ill, and some developed a distinctive skin rash just before other symptoms appeared. From these clues, the researchers suspected that deer ticks, common arachnids the size of a pinhead, were involved in transmitting an unknown infectious microbe.

Discovery of the Culprit

In 1981, as NIAID researchers were examining deer ticks for microbes that cause tick-borne disease, the researchers serendipitously found a new microbe. This spiral-shaped bacterium later was named Borrelia burgdorferi, after the NIAID scientist, Dr. Willy Burgdorfer, who discovered the microbe. The next year, NIAID researchers at the Rocky Mountain Laboratories isolated B. burgdorferi from deer ticks and developed a method to grow it in the laboratory. When scientists mixed the bacterium with blood from people who had recovered from Lyme disease, they found that the microbes reacted with a particular antibody produced during the immune response to infection. Such antibodies were not present in people who had never had Lyme disease, indicating that B. burgdorferi was the likely cause of Lyme disease. In further tests, rabbits developed both a rash similar to the typical Lyme disease rash as well as the same type of immune response generated after being bitten by ticks infected with B. burgdorferi. The following year, NIAID-supported scientists found B. burgdorferi in the blood and other tissues of patients with Lyme disease.

In the mid-1980s, NIAID-supported and other researchers began to decipher the makeup of the surface proteins of the microbe and made an important discovery. They identified and analyzed a protein on the outer surface of B. burgdorferi. This protein, outer surface protein A (OspA), causes an immune response in humans. NIAID researchers then cloned the gene for OspA and created recombinant OspA (rOspA). rOspA is an artificially manufactured version of the natural OspA. This technique allows the protein to be produced in large enough quantities for use in vaccine studies. In the early 1990s, NIAID investigators and their collaborators found that antibodies against OspA were able to neutralize B. burgdorferi in infected ticks, thus preventing the transmission of infection from ticks to humans. As basic research continued, other outer surface proteins as well as other parts of B. burgdorferi were identified as potential candidate vaccines.

Development and Abrupt End of a Vaccine

Since these surface proteins produce an immune response, researchers began to consider using them to develop vaccines against Lyme disease. In the early 1990s, NIAID-supported researchers developed an OspA-based vaccine that protected mice from infection.

Between 1995 and 1998, a vaccine based on rOspA, the component first made by NIAID investigators, was tested by SmithKline Beecham in humans. The vaccine was proven safe and effective for preventing infection for people between the ages of 15 and 70. In 1998, the FDA approved a vaccine against Lyme disease, LYMErix, produced by SmithKline Beecham. In 2001, the FDA withdrew the vaccine from the market due to debilitating side effects.

Recommended Books:
Surviving Lyme Disease Using Alternative Medicine by David A. Jernigan
Outwitting Ticks : The Prevention and Treatment of Lyme Disease by Susan Carol Hauser
Everything You Need to Know About Lyme Disease and Other Tick-Borne Disorders by Karen Vanderhoof-Forschner

Source:  Adapted from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD  20892, January 2000 (updated April 2002).