763. Discovery of OspA-specific human monoclonal antibodies reactive against a broad range of Borrelia species for the prevention of Lyme disease
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 763_IDWPOSTER.pdf (268.5 kB)
  • Background: Antibody to outer surface protein A (OspA) of Borrelia burgdorferi (sensu latu) prevents tick transmitted infection of Lyme disease in animal models and is the best serologic correlate of vaccine mediated protective immunity in humans.

    Methods: To develop a monoclonal antibody for pre-exposure prophylaxis (PrEP) of Lyme disease, we created a panel of borreliacidal human monoclonal antibodies (HuMabs) by immunizing mice that were transgenic for human immunoglobulin genes and inactivated mouse immunoglobulin genes with OspA protein of B. burgdorferi

    Results: Over 93 unique HuMabs bound to OspA and were tested in borreliacidal assays against Borrelia burgdorferi, B. afzelii and B. garini.  Four HuMabs (221-7, 857-2, 319-44, and 212-55) were selected as lead candidates based on high borreliacidal activities (<10 nM of IC50).  HuMab 319-44, 857-2 and 212-55 were borreliacidal against one or two species, whereas 221-7 was cidal (IC50 <10nM) against all three species.  Partial epitope mapping for the four lead HuMabs was performed by ELISA reactivity with OspA truncations and competition with LA-2.  HuMab 221-7 and 857-2 recognized a conformational epitope comprising a.a. 71-141, a relatively conserved region of OspA.  HuMab 212-55 bound to an epitope within a.a. 142-273.  HuMab 319-44 was found to bind within a.a. 178-273 and blocked LA-2 binding.  Alanine scanning mutagenesis of the LA-2 binding site defined a.a. D249 and S250 to be within the 319-44 epitope.  Surface plasmon resonance analysis revealed high affinity binding of all four HuMabs with OspA from B. burgdorferi.  HuMab 221-7 bound strongly to OspA from all three Borrelia species with affinity of <10nM.   Two HuMabs 319-44 and 221-7 were selected for further study in vivo and both prevented infection of mice challenged with B. burgdorferi-infected ticks.

    Conclusion: These studies suggest that OspA-specific HuMabs could provide PrEP from Lyme disease caused by a broad range of Borrelia species.

    Yang Wang, MD PhD, Naomi Boatright, BA, Andrew Sadowski, BA, William Thomas Jr., PhD and Mark S. Klempner, MD, MassBiologics of the University of Massachusetts Medical School, Boston, MA

    Disclosures:

    Y. Wang, None

    N. Boatright, None

    A. Sadowski, None

    W. Thomas Jr., None

    M. S. Klempner, None

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