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Lyme Disease NIH INfo 2012

Lyme Disease

Finding the Cause of Lyme Disease

Willy Burgdorfer, Ph.D., seen here inoculating ticks, discovered the spirochete, or corkscrew-shaped bacterium, that causes Lyme disease. The spirochete was later named for Dr. Burgdorfer: Borrelia burgdorferi. Credit: NIAID/RML

Borrelia burgdorferi, the bacterium that causes Lyme disease, was first isolated in 1982 by Willy Burgdorfer, Ph.D., a zoologist and microbiologist at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana. The following is a brief history of this groundbreaking discovery.

Lyme disease was first recognized in 1975 after researchers investigated why unusually large numbers of children were being diagnosed with juvenile rheumatoid arthritis in Lyme, Connecticut, and two neighboring towns. After considering several causative possibilities, such as exposure to airborne and waterborne microbes, researchers focused their attention on deer ticks. Investigators realized that most of the affected children lived and played near wooded areas. They also knew that the children’s first symptoms typically started during summer—the height of the tick season. Several patients reported having a skin rash just before developing their arthritis, and many recalled being bitten by a tick at the rash site.

About 2,000 miles away at RML, Dr. Burgdorfer was studying Rocky Mountain spotted fever. Dr. Burgdorfer was trying to help Jorge Benach, Ph.D., find the cause of more than 100 cases of spotted fever that occurred in New York from 1971 to 1976. Dr. Benach, of the New York State Health Department, had been a source of American dog ticks for Dr. Burgdorfer to study.

Some 30 years earlier, while a college student in Basel, Switzerland, Dr. Burgdorfer began his studies of tickborne diseases and focused on relapsing fever. This bacterial disease was spread by fast-feeding, soft-bodied ticks that sent infectious corkscrew-shaped spirochetes into their blood-meal hosts. At the time of Dr. Burgdorfer’s collaboration with Dr. Benach, spirochetes in slow-feeding, hard-bodied ticks—such as the deer tick or American dog tick—were rarely found.

In the summer of 1977, Allen C. Steere, M.D., was involved investigating Lyme disease cases for the Yale University School of Medicine. Twice he contacted Dr. Burgdorfer to discuss methods of evaluating, dissecting, and preserving ticks and tissues. During their conversations, Dr. Steere alluded to the deer tick as the likely vector for Lyme disease.

The following year, during a research sabbatical in Switzerland where he continued his tick studies, Dr. Burgdorfer noticed movement between the cells and tissue of six ticks he dissected. The movement came from larvae that were developing into a parasite found in deer.

Here is how all the preceding clues came together, as shared by Dr. Burgdorfer in a 1993 article he wrote for Clinics in Dermatology. Following his sabbatical, Dr. Burgdorfer resumed his Rocky Mountain spotted fever collaboration with Dr. Benach. None of the American dog ticks studied had helped resolve their mystery, so eventually Dr. Burgdorfer suggested they try studying a new tick vector, the deer tick. In October 1981, while testing more than 100 deer ticks that Dr. Benach supplied from Shelter Island, New York, Dr. Burgdorfer noticed in two ticks the same larvae-type movement that he had observed during his 1978 sabbatical.

Borrelia burgdorferi, seen here magnified 400 times, is transmitted to humans by the bite of an infected deer tick. Credit: CDC

While investigating the source of the movement, his attention was shifted to something new: long, coiled microorganisms that looked like spirochetes. But deer ticks were the hard species, not known to carry spirochetes. Dr. Burgdorfer recalled a 1949 conference he attended where attendees discussed a little-supported theory on Ixodidae—the family of hard ticks—spreading spirochetes and causing a European skin disorder.

Within hours of spotting and confirming the presence of spirochetes in the deer ticks, Dr. Burgdorfer dissected the remaining 124 ticks and found 75 with spirochetes. He cautiously wondered if he had found the cause of both the European skin disorder—erythema migrans—and Lyme disease. After notifying Dr. Benach and receiving serum from recovering Lyme disease patients, Dr. Burgdorfer and his colleagues found antibodies in the patient serum that reacted to spirochetes they had found in the deer ticks.

Further, Dr. Burgdorfer was assisted by RML colleague Alan Barbour in growing the spirochetes in a test tube using tissue from four of the infected deer ticks he had dissected. That exercise was successful, and in late November 1981, the scientists had found the cause of both Lyme disease and the European skin disorder. The study is in the June 18, 1982, edition of Science. For his role, the Lyme-causing spirochete was named for Dr. Burgdorfer: Borrelia burgdorferi.

Diagnostic Research

There is a great need to develop simple and rapid tests to determine whether people are infected with Borrelia burgdorferi, the bacterium that causes Lyme disease. NIAID is committed to improving Lyme disease diagnostics by supporting innovative research projects.

Priorities include finding potential targets—substances that new diagnostic tools might measure in patient samples—and improving the sensitivity and specificity of currently available diagnostic tests, thereby leading to more accurate results.

Important Considerations

Lyme disease can be difficult to diagnose for a number of reasons. Many of the common symptoms associated with the disease, such as headaches, dizziness, and joint/body pain, also occur with other diseases. The most distinct symptom of Lyme disease—the circular red rash known as erythema migrans (EM)—does not appear in at least one quarter of people who are actually infected with Lyme bacteria. Also, current diagnostic tests do not always detect early Lyme disease. Because treatment is generally more effective in early stages of the disease, it is important to develop new tools that can help doctors make an early diagnosis.

Doctors need to know whether a patient has an active infection, or has been exposed to the Lyme bacteria earlier in their life. Today's diagnostic tests have some limitations that make a clear, quick diagnosis difficult.

Lyme antibody tests—the most common diagnostic tool available today—look for antibodies in the blood that show a person has been exposed to B. burgdorferi. But it can take a few weeks before a person's immune system creates measurable levels of antibodies. This gap between being infected with the bacteria and the body's creation of antibodies can result in a false negative test for those with very early Lyme disease, resulting in a delay in treatment.

Conversely, it is possible to receive a false positive test when a person does not actually have Lyme disease. Unfortunately, other bacterial infections may mistakenly be reported as a positive Lyme antibody test. These issues highlight the need for diagnostic tools that can distinguish between Lyme and other bacteria, and can find evidence of Lyme disease soon after infection.

Current Diagnostic Approaches

To diagnose Lyme disease, a healthcare provider usually uses laboratory tests approved by the Food and Drug Administration (FDA) combined with information about a patient’s symptoms.

The Centers for Disease Control and Prevention (CDC) currently recommends a two-tiered testing approach: a conventional enzyme-linked immunoassay (ELISA) test, followed by a Western Blot test. The ELISA is a blood test that detects antibodies but does not test for B. burgdorferi itself. A positive result from this first-level screening may suggest current or past infection. The ELISA is designed to be very “sensitive,” meaning that almost everyone who has Lyme disease (and some people who do not) will test positive. If the screening test is negative, it is highly unlikely that the person has Lyme disease, and no further testing is recommended. If the screening test is positive or inconclusive, a Western blot test should be performed to confirm the results.

Used appropriately, the Western blot test is designed to be “specific,” meaning that it will usually be positive only if a person has been truly infected by B. burgdorferi. If the Western blot is negative, it suggests that the ELISA test was a false positive.

The Centers for Disease Control and Prevention (CDC) does not recommend testing by Western blot without first using the ELISA. Using the Western blot on its own makes a false positive result more likely. Such results may lead to people being treated for Lyme disease when they do not have it, instead of being treated for the true cause of their illness.

Other Diagnostic Tests for Lyme Disease

Some laboratories offer Lyme disease testing using urine or other body fluids. These tests are not approved by the Food and Drug Administration (FDA) because they have not been proven to be accurate. For example, one study of urine-based polymerase chain reaction (PCR) assays for Lyme disease diagnosis showed that with currently available tools, urine cannot be used to accurately diagnose Lyme disease. Another study by NIAID-supported scientists showed that the Lyme Urinary Antigen Test (LUAT) was unreliable and resulted in excessive numbers of false positives. In the same study, researchers confirmed that an ELISA followed by a Western blot test was nearly 100 percent reliable in diagnosing Lyme disease (Am J Med 110: 217, 2001).

Current Research on New Approaches

NIAID actively supports research on Lyme disease diagnostics. Small businesses and public/private partnerships often submit applications for new research projects. NIAID grantees also work directly with CDC scientists to evaluate and compare the effectiveness of currently used diagnostic methods.

Working with CDC, NIAID plays a major role in encouraging the development of new approaches to improve Lyme disease diagnosis in people with co-infections such as the tickborne infections anaplasmosis or babesiosis. New diagnostic tests are also needed to distinguish between people with B. burgdorferi infection and those whose immune responses stem solely from past Lyme disease vaccination. Although Lyme disease vaccines for humans are no longer available in the United States, the discontinued LYMErix vaccine used between 1998 and 2002 was based on a specific part of B. burgdorferi called outer surface protein A (OspA). In response to the vaccines, immunized individuals developed antibodies for OspA. Because the conventional ELISA measures OspA antibodies to determine if someone has Lyme disease, the test does not provide accurate results for immunized individuals. People who received the vaccination will test positive whether or not they are actually infected with B. burgdorferi.

NIAID grantees have shown that C6, a synthetic peptide 26 amino acids long that is derived from the B. burgdorferi surface antigen, VlsE, can be used in a rapid and sensitive ELISA test for Lyme disease diagnosis. In contrast to the conventional ELISA, this diagnostic test does not detect antibodies for OspA. Therefore, the FDA-approved C6 ELISA can be used for those who received the OspA-based LYMErix vaccine (J Clin Microbiol 40: 2591, 2002).

NIAID-supported investigators are now working closely with CDC to determine if the C6 ELISA can eventually replace the two-step standard ELISA and Western blot tests (Clin Immunol 132(3): 393, 2009). Other projects are investigating the development of blood-based diagnostics to detect a range of tickborne infections using a single test, as well as the continued search for Lyme disease antigens that may help doctors determine when an infection has been cured.

Future Possibilities for Diagnostic Tools

NIAID-supported scientists have identified genome sequences for multiple strains of B. burgdorferi. Greater advances in diagnostics are anticipated as genetic information is combined with advances in microarray technology, imaging and proteomics. These growing fields of science are expected to lead to improved diagnostic tools as well as provide new insights on the pathogenesis of Lyme disease.


The Problem

Ticks can become infected with more than one disease-causing microbe (called co-infection). Co-infection may be a potential problem for humans, because the Ixodes ticks that transmit Borrelia burgdorferi, the bacteria which causes Lyme disease, often carry and transmit other pathogens, as well. A single tick could make a person sick with any one—or several—diseases at the same time. Possible co-infections include Lyme borreliosis, anaplasmosis and babesiosis. In Europe and Asia, Ixodes ticks also are known to transmit tickborne encephalitis viruses. Fortunately, this tickborne viral infection has not yet been reported in the United States, although in rare instances, ticks have been found to be co-infected with B. burgdorferi and Powassan virus.

Nymphal and Adult Ticks Shown to be Co-Infected: Studies to Understand Potential Relation to Human Disease Underway

Studies have looked at co-infection rates at different points in the tick’s life cycle. In a comprehensive review of 61 different published reports, Nieto and Foley found that 2 to 5 percent of young nymphal I. scapularis ticks were reported to be co-infected with more than one microbe. Adult tick co-infection rates with B. burgdorferi varied widely between 1 to 28 percent across the reports analyzed (Vector Borne Zoonotic Dis. 9(1):93-101, 2009). Although humans are more likely to be bitten by the smaller nymphal stage ticks (CDC), co-infection rates in adult ticks may provide important information about how tickborne diseases are transmitted.

Co-infection by some or all of these other microbes may make it more difficult to diagnose Lyme disease. Being infected by more than one microbe might also affect how the immune system responds to B. burgdorferi (J Infect Dis. 186: 428, 2002). NIAID-supported studies of mice found that co-infection with human granulocytic ehrlichiosis—which is now known as anaplasmosis—results in more severe Lyme disease (Infect Immun. 69: 3359, 2001). By contrast, when mice were co-infected with B. microti and B. burgdorferi, neither microbe affected how each individual infection progressed. (J Infect Dis. 192: 1634, 2005).

Another study looked at the tissues of mice infected with both B. burgdorferi and Anaplasma phagocytophilium, the bacterium that causes anaplasmosis in humans. Scientists found increased numbers of B. burgdorferi in the ears, heart, and skin of co-infected mice; however, the numbers of A. phagocytophilium remained relatively constant. The co-infected mice produced fewer antibodies for A. phagocytophilium, but not for B. burgdorferi. These findings suggest that co-infection can affect the amount of microbes in the body and antibody responses (Infect Immun. 73: 3440, 2005).

Clinical Studies

In NIAID-supported clinical studies on Lyme disease, patients with persisting symptoms were examined to determine if they might have been co-infected with other tickborne infectious diseases at the time of their acute episode of Lyme disease. In one clinical study, babesioisis (B. microti), granulocytic ehrlichiosis (Anaplasma phagocytophilia), and tickborne encephalitis virus infection were evaluated. The study found that 2.5 percent of blood samples showed signs of B. microti and 8.6 percent had evidence of A. phagocytophilia. None of the patients examined were found to be positive for tickborne encephalitis viruses (Vector Borne Zoonotic Dis. 2: 255, 2002). In this study, the persistence of symptoms in the vast majority of patients with "post-Lyme syndrome" could not be attributed to co-infection with one of these microbes.

How co-infection might affect disease transmission and progression is not known, but could be important in diagnosing and treating of Lyme and other tickborne diseases. Further analysis is underway through NIAID-supported projects to better understand co-infection rates in nymphal ticks, as well as rates of co-infections in Lyme disease human patients.

Antibiotic Treatment

For early Lyme disease, a short course of oral antibiotics, such as doxycycline or amoxicillin, cures the majority of cases. In more complicated cases, Lyme disease can usually be successfully treated with 3 to 4 weeks of antibiotic therapy.

After being treated for Lyme disease, some patients still report non-specific symptoms, including persistent pain, fatigue, impaired cognitive function, or unexplained numbness. These patients often show no evidence of active infection and may be diagnosed with post-Lyme disease syndrome (PLDS). In patients with PLDS, studies have shown that more antibiotic therapy is not beneficial and the risks outweigh the benefits.

Clinical Studies

In an effort to address the confusion regarding appropriate therapy, NIAID has funded three placebo-controlled clinical trials to learn more about the efficacy of prolonged antibiotic therapy for treating PLDS. The published results were subjected to rigorous statistical, editorial, and scientific peer review.

These trials were designed to ensure that several key parameters were addressed:

·         The susceptibility of B. burgdorferi, the bacterium that causes Lyme disease, to specific antibiotics

·         The ability of antibiotics to cross the blood-brain barrier, access the central nervous system, and persist at effective levels throughout the course of therapy

·         The ability of antibiotics to kill bacteria living both outside and inside mammalian cells

·         The safety and welfare of patients enrolled in the trials

The first clinical trial, which included two studies conducted at multiple research sites, provided no evidence that extended antibiotic treatment is beneficial (New Engl J Med 345: 85-92, 2001). In those studies, physicians examined long-term antibiotic therapy in patients with a well-documented history of previous Lyme disease, but who reported persistent pain, fatigue, impaired cognitive function, or unexplained numbness. Patients were treated with 30 days of an intravenous antibiotic followed by 60 days of treatment with an oral antibiotic.

These studies did reinforce the evidence that patients reporting PLDS symptoms have a severe impairment in overall physical health and quality of life. However, prolonged antibiotic therapy showed no benefit when compared with groups who received placebo.

In another study, published in 2003, researchers examined the effect of 28 days of intravenous antibiotic compared with placebo in 55 patients reporting persistent, severe fatigue at least 6 months following treatment for laboratory-diagnosed Lyme disease. Patients were assessed for improvements in self-reported fatigue and cognitive function (Neurology 60: 1923-30, 2003).

In that study, people receiving antibiotics did report a greater improvement in fatigue than those on placebo. However, no benefit to cognitive function was observed. In addition, six of the study participants had serious adverse events associated with intravenous antibiotic use, and four patients required hospitalization. Overall, the study authors concluded that additional antibiotic therapy for PLDS was not supported by the evidence.

More recently, a study supported by the National Institute of Neurological Disorders and Stroke (NINDS), also a part of the National Institutes of Health, again showed that long-term antibiotic use for Lyme disease is not an effective strategy for cognitive improvement (Neurology 70(13): 992-1003, 2008). Researchers compared clinical improvement following 10 weeks of intravenous ceftriaxone versus intravenous placebo. The patients were treated for Lyme disease and presented with objective memory impairment tests. In a complicated statistical model, the ceftriaxone group showed a slightly greater improvement at 12 weeks, but at 24 weeks, both the ceftriaxone and the placebo groups had improved similarly from baseline. In addition, adverse effects attributed to intravenous ceftriaxone occurred in 26 percent of patients. The authors concluded that because of the limited duration of the cognitive improvement and the risks involved, 10 weeks of intravenous ceftriaxone was not an effective strategy for cognitive improvement in these patients, and more durable and safer treatment strategies are still needed.

For more information, please see the Chronic Lyme Disease section.

Animal Models

Animal models have provided considerable information on the transmission and pathogenesis of Lyme disease, as well as on the mechanisms involved in the development of protective immunity. Studies of the effects of antibiotic therapy in animals infected with B. burgdorferi have been conducted most often with mice, but also with hamsters, gerbils, dogs, and non-human primates. (see Wormser and Schwartz, Clin Microbiol Rev 22(3): 387-395 for a recent review).

NIAID-supported studies have shown that B. burgdorferi can be detected in mice for at least 3 months after treatment with therapeutic doses of various antibiotics (ceftriaxone, doxycycline, or azithromycin). These surviving bacteria could not be transmitted to healthy mice, and some lacked genes associated with infectivity. By 6 months, antibiotic-treated mice no longer tested positive for the presence of B. burgdorferi, even when their immune systems were suppressed. Nine months after antibiotic treatment, low levels of Borrelia DNA still could be detected in some—but not all—of the mice (J Infect Dis 186: 1430, 2002). These findings indicate that noninfectious B. burgdorferi can persist for a limited period of time after antibiotic therapy. The implications of these findings to persistent infection and the nature of PLDS in humans still need to be evaluated.

In a 2008 study, mice were treated with the antibiotic ceftriaxone for 1 month following either early or later stages of infection with B. burgdorferi. After completing antibiotic treatment, tissues from the mice were analyzed using a variety of scientific methods. B. burgdorferi could not be grown in cell cultures for any of the mice treated with antibiotic. In a small number of the treated mice, however, bacteria were detected in their tissues. Further, when Ixodes scapularis ticks fed on some of the antibiotic-treated mice, the ticks were able to transmit the bacteria to mice with weakened immune systems who were not previously infected with B. burgdorferi. Highly sensitive laboratory tests were able to detect the presence of B. burgdorferi in these mice. However, the bacteria did not grow in cell cultures (Antimicrob Agents Chemother 52: 1728-1736). The implications of these findings to persistent infection and the nature of PLDS in humans are yet to be fully understood. NIAID continues to support further studies of B. burgdorferi persistence after antibiotic treatment in specific animal models.

NIAID, in collaboration with NINDS, supported comprehensive studies on non-human primates looking at the neuropathology associated with post-Lyme disease syndrome (Ann Neurol 56: 361, 2004). A major goal of these studies was to optimize the Rhesus monkey model of Lyme disease as well as to determine the pathogenesis of the disease with a focus on its neurological manifestations.

The results of these studies have expanded the knowledge of those factors that contribute to the pathology associated with B. burgdorferi infection of the central nervous system. Among the findings:

·         Non-human primates are easily infected with low levels of B. burgdorferi through skin injection. In healthy non-human primates, the infection is transient and rapidly cleared as the animals developed antibodies to fight off infection. However, in non-human primates with suppressed immune systems, infection persists and involves the central and peripheral nervous systems, as well as organs, such as the heart, bladder, skin, and skeletal muscle (Clin Diagnostic Lab Immunol. 8: 225, 2001; Ann. Neurol. 50: 330, 2001; Infect Immun 71: 7087, 2003).

·         The presence of the bacteria’s genetic material was particularly prevalent in the central nervous systems of infected non-human primates compared to other tissues (Proc Natl Acad Sci 100: 1953, 2003; Microbial Path 39: 27, 2005).

·         The pattern of infection is dependent upon the strain of Borrelia used to induce infection; B. garinii induces a different type of disease in mice and non-human primates than does B. burgdorferi (Ann Neurol 54: S49, 2004).

The Role of Autoimmune Reactivity

The results of recent studies conducted by NIAID and intramural scientists from the National Institute of Neurological Disorders and Stroke indicate that T cells from patients with chronic Lyme disease are reactive not only against Borrelia burgdorferi-specific antigens but also against various host (self) antigens (Nature Med, 5:1375, 1999). Such antigenic mimicry might generate autoimmune inflammatory reactions that could be responsible for arthritic as well as some neurological symptoms associated with chronic Lyme disease. Intramural and extramural scientists are exploring the implications of this finding.

Antibodies against the OspA epitopes of B. burgdorferi also have been shown to cross react with neural tissue (J Peripheral Nervous System. 9:165, 2004; J Neuroimmunol. 159:192, 2005) as well as myocin (J Clin Microbiol. 43:850, 2005). Such antigenic mimicry may have the potential to generate autoimmune inflammatory reactions that could be responsible for the neurological symptoms associated with chronic Lyme disease. Intramural and extramural scientists are evaluating this possibility in greater detail. In this context, it is interesting to note that homologies between proteins of B. burgdorferi and thyroid antigens also have been reported (Thyroid. 14:964, 2004).

In clinical studies conducted by NIAID-supported extramural scientists, case subject patients with post-treatment chronic Lyme disease (PTCLD) were compared to control subjects without such symptoms for the presence of several human leukocyte antigen (HLA) class II (DRB1 and DQB1) genetic markers, some of which are known to be associated with the expression of autoimmune reactivity. The results obtained did not support the involvement of an autoimmune mechanism in PTCLD (J Infect Dis. 192:1010, 2005). However, since not all autoimmune diseases are associated with specific HLA haplotypes, these findings do not necessarily exclude that possibility. Definitive proof clearly would involve demonstrating the presence of significant levels of relevant autoimmune antibodies and/or autoreactive T cells in patients with PTCLD, but not in treated control subjects without such symptoms. A greater frequency of DRB1*0401, which has been reported to be associated with antibiotic-treatment resistant arthritis (Science. 281:703, 1998) was noted in the case subject patients. Although this finding appeared to be nominally significant (p <0.05), its biological significance is ambiguous since none of the case subjects considered had symptoms of inflammatory arthritis.



Two large pharmaceutical companies have devoted considerable effort to developing a vaccine for Lyme disease, but there are no vaccines for humans available in the United States today.

Double-blind, randomized, placebo-controlled clinical trials—the most rigorous type of clinical trial used today— have been completed for each of two Borrelia burgdorferi vaccines manufactured by GlaxoSmithKline [(GSK), formerly SmithKline Beecham (SKB)], and Pasteur Merieux Connaught. Each study involved more than 10,000 volunteers from areas of the United States where Lyme disease is common.

Both vaccines were based on a specific part of B. burgdorferi called outer surface protein A (OspA). They were found to be between 49 and 68 percent effective in preventing Lyme disease after two injections, and 76 to 92 percent effective in preventing Lyme disease after three injections. The duration of the protective immunity generated in response to the vaccines is not known. The SKB vaccine was ultimately licensed as LYMErix and approved by the Food and Drug Administration (FDA) in December 1998.

NIAID was not directly involved in the design and implementation of these particular vaccine trials. However, patents for cloning the genes used in making the vaccine, as well as knowledge of how certain antibodies contribute to protective immunity, were derived from basic research grants funded by NIAID.

In April 2002, GSK announced that even with the incidence of Lyme disease continuing to rise, sales for LYMErix declined from about 1.5 million doses in 1999 to a projected 10,000 doses in 2002. Although studies conducted by FDA failed to reveal that any reported adverse events were vaccine-associated, GSK discontinued manufacturing the vaccine (Vaccine 20: 1603, 2002).

NIAID Research

Reservoir-based approaches

Infectious disease reservoirs are what scientists call the places or populations that harbor disease-causing pathogens. For example, certain types of wildlife can be long-term carriers, or hosts, of a disease. Rodents are a major reservoir for Lyme disease, so scientists have been looking at ways to prevent them from getting infected with B. burgdorferi. Stopping the bacterial infection in rodents could potentially prevent transmission of the bacteria to the ticks that depend on the rodents in their early life cycle, and, therefore, from ticks to humans.

NIAID-funded investigators have developed an experimental bait—and vaccine—delivery system. In a study, mice were given this vaccine-laced bait then exposed to Ixodes ticks carrying multiple strains of B. burgdorferi. Oral vaccination was found to protect 89 percent of the mice from infection and the blood tests showed their immune systems created antibodies to the Lyme bacteria.

NIAID is part of a collaborative effort with researchers at Ventria Bioscience and the Centers for Disease Control and Prevention who are supporting a similar approach. Scientists are working to grow rice plants that contain vaccine elements that could eventually be fed to rodent populations, thus blocking the transmission cycle of the disease from rodents to ticks to people. These findings are consistent with the results reported by other investigators (Proc Natl Acad Sci 52: 18159, 2004).

In other studies, NIAID grantees have developed a mouse-targeted vaccine using Vaccinia virus. Oral vaccination of mice with a single dose of the vaccine resulted in strong immune system response and full protection from B. burgdorferi infection among vaccinated mice. In addition, scientists observed a significant clearance of B. burgdorferi from infected ticks who fed on vaccinated mice (Vaccine 24: 1949, 2006). These findings indicate that such a vaccine may effectively reduce the incidence of Lyme disease in endemic areas.

Human Vaccine Development

NIAID supports significant research efforts focused on human vaccination against Lyme disease. Ongoing research projects include the development of a new, second-generation vaccine for human Lyme disease; studies to test the vaccine in mice are underway. NIAID also supports multiple research projects in early-stage discovery and characterization of novel vaccine targets.