With hundreds of thousands of people in the United States diagnosed with Lyme disease each year, researchers are looking for new ways to prevent infection and treat the disease.
A team led by Yi-Pin Lin , associate professor in the Department of Infectious Disease and Global Health at Cummings School of Veterinary Medicine at Tufts University , has received a $4 million National Institutes of Health grant to advance development of a Lyme disease vaccine and new therapies for early infection.
The research builds on a previous study showing that an engineered version of a protein called CspZ generated a strong immune response and protected mice against Borrelia burgdorferi , the bacterium that causes Lyme disease. CspZ acts as a molecular shield, helping Borrelia burgdorferi disable a critical component of the host’s first-line immune defenses. Lin and his colleagues modified the protein to expose a hidden vulnerable region, allowing the immune system to recognize it and produce antibodies that target the bacterium.
Now, the researchers want to understand exactly how antibodies triggered by the vaccine stop Borrelia burgdorferi —knowledge that could help them improve the potential vaccine and identify new treatments.
“It is not yet known if the antibodies directly kill the bacterium, block essential biological functions, prevent the pathogen from establishing infection, or recruit other immune components to eliminate it,” said Lin. “Identifying these mechanisms could reveal the specific qualities that future Lyme disease vaccines should induce.”
To investigate what generates protective immunity, the five-year project will bring together collaborators with complementary expertise.
Baylor College of Medicine researchers will generate and characterize monoclonal antibodies against CspZ. These lab-made proteins that mimic the body’s natural immune response will serve as powerful tools to help determine which antibody features are essential for protection—and how those protective responses can be enhanced through vaccination.
The Institute for Systems Biology will bring an advanced technique (proteomics-based cross-linking mass spectrometry) to pinpoint exactly where protective antibodies bind to CspZ. This will provide the molecular blueprint for designing improved vaccines capable of eliciting stronger and broader protective immune responses.
Klemen Strle , research assistant professor of molecular biology and microbiology at Tufts University School of Medicine , will use blood samples from people previously infected with Lyme disease to further investigate how the engineered antibodies work against the bacterium in humans.
“Our hope is that our findings will help unlock new knowledge about the protective immunity of CspZ-based vaccines and reveal new vulnerabilities in Borrelia burgdorferi that could be targeted by future treatments,” said Lin, who, along with Strle, is part of the Tufts University Lyme Disease Initiative .