Vaccinating mice against Lyme disease could help reduce the risk of transmission of the disease to humans

Vaccinating large populations of white-footed mice against the bacterium that causes Lyme disease could help reduce the risk of transmission of the disease to humans, says a study supported by the National Institute of Allergy and Infectious Diseases (NIAID).

The findings, scheduled to be published online this week in Proceedings of the National Academy of Sciences, demonstrate that vaccination of wildlife hosts may be a promising ecologically based strategy to help prevent the spread of infectious diseases to humans by vectors such as insects and ticks.

"This 'proof-of-principle' study demonstrates that vaccinating a carrier of a vector-borne disease in the wild is a potential method for preventing transmission of that disease to humans," says Anthony S. Fauci, M.D., NIAID director. "When integrated with other protective measures, this strategy could have significant implications, not only for preventing Lyme disease, but for preventing other vector-borne diseases as well, including plague and West Nile virus."

"The targeted vaccination of wildlife carriers could offer more far-reaching protection against vector-borne diseases than vaccinating humans," adds Alan Barbour, M.D., professor of microbiology and molecular genetics and medicine with the University of California, Irvine, and senior author on the paper. "When the vaccine is targeted to humans, only those who experienced a satisfactory immune response to the vaccine are protected; however, when the vaccine is targeted to wildlife carriers, the risk of infection is lowered for everyone in the community."

Lyme disease is the leading cause of vector-borne illness in the United States. Approximately 23,000 cases of Lyme disease were reported in the United States in 2002. The disease is caused by Borrelia burgdorferi, a spiral-shaped bacterium spread through the bite of a blacklegged tick. Symptoms can include a characteristic "bull's-eye" rash known as erythema migrans, as well as fatigue, chills and fever, headache, muscle aches and joint pain. Early treatment prevents the development of more debilitating symptoms. Lyme disease is most commonly found in the northeastern, mid-Atlantic and upper north-central regions of the United States, as well as parts of northwestern California.

In their study, the research team took aim at the larval form of the blacklegged tick, the crucial stage during which a tick becomes infected with B. burgdorferi. Normally, uninfected tick larvae pick up the bacterium the first summer of their two-year life cycle while taking their first blood meal from infected small animals, such as the white-footed mouse. The white-footed mouse is considered a key animal reservoir for Lyme disease. One year later, after the larva develops into a nymph, it feeds on a second animal host, possibly a human, infecting that host. Roughly 90 percent of human infections are contracted from nymphal ticks.

The researchers' goal was to reduce the level of B. burgdorferi infection in nymphal ticks. By vaccinating a large sample of white-footed mice, the researchers hypothesized, fewer tick larvae would become infected the first summer and, in turn, fewer nymphs would be capable of transmitting the disease to humans the following summer.

Throughout the summers of 1998 and 2001, researchers trapped and vaccinated a total of more than 900 mice in 12 different forested sites in Connecticut--six unique sites each summer. In half of the sites, mice received injections of active vaccine; in the other six sites, mice received a placebo.

The vaccine contained a recombinant protein--called OspA--normally found on the outer surface of B. burgdorferi in ticks but not in mice. The vaccine is based on one previously used in humans and currently used in dogs. When an infected nymph feeds on an immunized mouse, the animal's antibodies kill the bacterium inside the nymph, preventing the nymph from transmitting the disease.

After immunizing roughly 55 percent of the mouse population over the course of the two studies, researchers saw an overall reduction of 16 percent in the prevalence of nymphal infection at locations in which mice had been given vaccine versus placebo. This translates to a possible reduction of 27 percent in nymphal infection had all the mice been vaccinated.

In addition, the researchers concluded that other animals, such as chipmunks and shrews, may play a larger role in the spread of Lyme disease than was previously thought. For example, the researchers discovered that the success of the vaccine in curbing the infection of nymphal ticks depended largely on mouse density. In sites where mouse densities were high, the numbers of infected nymphs in corresponding control sites were also high, indicating the important role mice played in nymphal infection prevalence in those sites. It was in these areas where the vaccine worked best in preventing nymphal infection the following year. In contrast, where mouse densities were lower, the vaccine was less effective in reducing the prevalence of nymphal infection, suggesting that other animals probably played a role in disease transmission. Also, the researchers found that certain strains of B. burgdorferi were less likely than other strains to be passed from a mouse to a tick; these strains were most prevalent in nymphs in one study site in which infection prevalence did not change following mouse immunization, again indicating the contribution of other animal reservoirs.

Which animals help spread Lyme disease, and, more specifically, which ones transmit the more virulent strains, needs further study, the researchers contend, to determine how best to implement a broad-based vaccination program. Also, study sites need to be monitored for strains that are not susceptible to the vaccine. Lastly, experiments will be conducted in which the vaccine is administered orally--the most logical way to vaccinate large numbers of animals--either as food pellets or in bait boxes targeted to certain species, much like the rabies vaccination program that has met with success in the United States and Europe. Such a vaccination program would be environmentally beneficial, say the researchers, because it would not detrimentally affect the ecology of a region.

Other collaborators on the study include Durland Fish, Ph.D., Yale University School of Medicine, and Jean Tsao, Ph.D., Michigan State University (formerly with University of Chicago and Yale).