Lisa BlumPrincipal Translational Scientist at NGM Biopharmaceuticals & Former Postdoctoral Fellow at Stanford University School of Medicine

Sequencing of Antibody Responses to Borrelia burgdorferi Infection – Generation of Recombinant Antibodies with Diagnostic and Therapeutic Utility

Despite the increasing incidence of Lyme disease in the US, a definitive diagnostic still does not exist, leaving the medical community to rely on the sub-optimal two-tier antibody tests. These tests measure the body’s memory response to Borrelia burgdorferi (Bb) infection. Given that the Bb bacteria changes it surface proteins so readily to avoid immune recognition, what is needed is a measurement of the body’s ongoing immune response. Such an analysis requires profiling of antibodies while they are still being formed.

Although several methods exist for profiling antibodies today, none are able to comprehensively characterize or rationally differentiate the antibodies most likely to drive protective immunity against Bb. To address this challenge, Dr. Blum is using a DNA barcoding technology her laboratory has already used successfully to characterize rheumatoid arthritis and influenza. She will use this technology to perform high-throughput sequencing of antibody repertoires in three sets of patients with Lyme disease: (i) early untreated Lyme, (ii) late untreated Lyme, and (iii) Post-treatment Lyme disease (PTLD). This effort should provide insights into why some patients have mild or acute symptoms, while others develop PTLD and become chronically ill. It will also yield monoclonal antibodies (mAbs) that could be useful as diagnostics and as passive immunotherapies to directly clear Bb infection or augment antibiotics. At the end of the 18-month study, Dr. Blum expects to produce recombinant mAbs, identify their binding targets, and select the top mAb candidates based on binding studies in the lab.

Dr. Blum received her BSc in Food Science and her Ph.D. in Immunology from Cornell University in the laboratory of Dr. Judith Appleton. She joined Dr. Bill Robinson’s laboratory in 2012 and has been applying the antibody sequencing technology to autoimmune diseases, pulmonary arterial hypertension and more recently Lyme.

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