DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Lyme Disease Awareness Month - Spotlight on TBDRP FY17 Lyme Disease Initiatives

Posted May 21, 2019

Dr. John Belisle, at Colorado State University
Dr. Troy Bankhead, at Washington State University
Dr. Nicole Baumgarth, at the University of California, Davis
Dr. Yang Wang, at MassBiologics, University of Massachusetts Medical School

In 2017 there were 29,513 confirmed and 13,230 probable cases of Lyme disease, representing a 17% increase from the previous year (1,2). Of the patients diagnosed with Lyme disease each year, a proportion of those individuals will complete treatment yet still suffer with debilitating symptoms, termed as Post-Treatment Lyme Disease Syndrome (PTLDS) (3). With PTLDS, patients experience continuous or relapsing symptoms possibly due to persistent bacterial infection with Borrelia burgdorferi, the causative agent of Lyme disease (3), or due to changes to their immune system. Moreover, while some patients are diagnosed and respond to treatment, there are additional populations of individuals that are undiagnosed, either because they do not present symptomatically and therefore do not seek treatment, or their clinical parameters do not meet the limit of detection with the current, time intensive, insensitive diagnostic assays or examinations.  Therefore, these cases remain unreported and, in essence, the true burden of Lyme disease remains unknown.

May is Lyme Disease Awareness Month which focuses on bringing the struggles of patients, their physicians, and their caregivers to the forefront of public attention. Since its inception in fiscal year 16 (FY16), the Congressionally Directed Medical Research Programs (CDMRP) Tick-Borne Disease Research Program (TBDRP) has received a $5 million Congressional appropriation each year to allocate through a two-tiered peer and programmatic review process to awardees focused on Lyme disease research or research on other  tick-borne disease (TBDs). Importantly, these awards address at least one of four TBDRP focus areas: diagnosis, treatment, prevention, and pathogenesis, which aim to lessen the burden of TBDs, to improve treatment options and diagnostic assays, or to investigate the pathogenic mechanisms of the causative agents of TBDs.

In FY17, there were four awards with a primary focus on Lyme disease. A brief summary of the overarching goals of these projects is described below.

Dr. John Belisle
Dr. John Belisle

Dr. John Belisle, at Colorado State University, is leveraging his expertise in the development of diagnostic tools, vaccines, and therapeutics for mycobacterial infections to propose developing a novel early Lyme disease diagnostic test. Funded in part by a FY17 TBDRP award, Dr. Belisle is investigating a noninvasive option for diagnosing Lyme disease using small molecule biosignatures, identified via liquid-chromatography mass spectrometry (LC-MS) of patient urine specimens, which would allow differentiation from other infections.  While TBDRP-funded studies using larger cohorts of adult and pediatric samples are ongoing, preliminary studies using a small cohort of samples from 28 adults (14 with Lyme disease and 14 healthy controls) have shown that LC-MS successfully identified a unique biosignature capable of correctly discriminating early Lyme disease from other patient controls with an accuracy of better than 70%. If successful, Dr. Belisle’s tool will provide the Lyme community with a new diagnostic tool, enabling faster intervention.




Dr. Troy Bankhead
Dr. Troy Bankhead

Dr. Troy Bankhead, at Washington State University, is focusing his work on the mechanisms of persistence and pathogenesis utilized by Borrelia burgdorferi. Specifically, Dr. Bankhead’s efforts are concentrated on mechanistic studies surrounding regulation of the VlsE lipoprotein, a known factor that contributes to bacterial immune evasion and persistence. This research team has previously developed pivotal research tools, including the mini vls-plasmid construct that can be used to study bacterial persistence. In his TBDRP-funded award, Dr. Bankhead aims to identify the genetic determinants required for vlsE gene expression and the effects of vlsE gene expression on antigenic variation, a bacterial tactic of immune evasion. His work will help the Lyme disease community better understand mechanisms of persistence and will potentially allow for targeting of vlsE in patients to prevent the development of persistent infections.



Dr. Nicole Baumgarth
Dr. Nicole Baumgarth

Dr. Nicole Baumgarth, at the University of California, Davis, is studying the mechanisms underlying immune responses to pathogens, in particular, influenza and Borrelia burgdorferi. Her recent efforts have sought to identify strategies of Borrelia burgdorferi immune evasion by addressing key questions surrounding the antibody-mediated response to infection. Dr. Baumgarth has previously shown that Borrelia burgdorferi infection inhibits the development of a functional immune response in its murine host. In her TBDRP-funded award, Dr. Baumgarth proposes to identify and characterize the host immune response, specifically murine and human IgG antibodies, to Borrelia burgdorferi infection. She aims to show that IgG antibodies produced in the presence of Borrelia are not fully functional and that changes in a patient’s IgG correlate with ongoing disease symptoms after treatment. If successful, Dr. Baumgarth’s work could pave the way for novel treatments as well as the identification of biomarkers for those patients at risk for developing PTLDS.



Dr. Yang Wang
Dr. Yang Wang

Dr. Yang Wang, at MassBiologics, University of Massachusetts Medical School, the only non-profit, FDA-licensed manufacturer of biologics, is utilizing her expertise in antibody-based therapeutics to develop a passive, pre-exposure immunoprophylaxis (PrEP) against Borrelia burgdorferi to protect susceptible populations against Lyme disease. As there is no current anti-Lyme prophylaxis available, Dr. Wang’s work is addressing a critical gap in the field. In this FY17 TBDRP-funded effort, Dr. Wang hypothesizes that human monoclonal antibodies possessing a long half-life and bactericidal activity against outer surface protein A (OspA), a protein specific to Borrelia Burgdorferi, could be an effective approach for PrEP. Over the course of the award, Dr. Wang will evaluate and validate the anti-OspA antibody via in-vivo animal challenge, passive transfer models, and tick feeding models utilizing human serum samples. If successful, Dr. Wang’s work could ultimately result in a PrEP product for Lyme disease and potentially reduce the overall burden of Lyme disease.





References

  1. https://www.cdc.gov/lyme/stats/graphs.html
  2. https://www.cdc.gov/lyme/datasurveillance/recent-surveillance-data.html
  3. https://www.cdc.gov/lyme/postlds/index.html

Links:

Public and Technical Abstracts:  Metabolic Biosignatures of Lyme Disease in Human Urine

Public and Technical Abstracts:  Mutational Analysis of Putative Regulatory Elements of the Antigenically Variable VlsE Protein of the Lyme Disease Spirochete

Public and Technical Abstracts:  Defining Protective and Disease-Reducing Immunity to Borrelia burgdorferi Infection

Public and Technical Abstracts:  Development of a Bactericidal, Long-Half-Life, OspA-Specific Human Monoclonal Antibody as a Novel Pre-exposure Prophylaxis (PrEP) for Lyme Disease 

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Last updated Thursday, May 23, 2019