764. Human monoclonal antibodies specific for OspA prevent Lyme borreliosis in mice
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 764_IDWPOSTER.pdf (199.1 kB)
  • Background: The incidence of Lyme disease is rapidly increasing each year with over 3,000,000 cases estimated by CDC in the United States. Prevention of Lyme disease with vaccine has been challenging and the only currently available means to prevent Lyme disease is to avoid exposure to infected ticks. 

    Methods: Since vaccine-induced antibodies against outer surface protein A (OspA) correlated with protection from infection with Borrelia burgdoferi, we studied immune mediated pre-exposure prophylaxis (PrEP) by human monoclonal antibodies (HuMabs) against OspA in a robust murine model of tick transmitted Lyme disease. 

    Results: Two HuMAbs (221-7 and 319-44), which recognize distinct epitopes, were selected as lead candidates from a panel of 93 unique HuMAbs to OspA  based on potent in vitro borreliacidal activity and breath of reactivity with several species of Borrelia.  The protective efficacy of these two HuMabs was evaluated in a murine model of tick-mediated transmission of B. burgdorferi. Groups of five C3H mice were treated with anti-OspA HuMabs, or a control HuMAb, at 1-10 mg/kg i.p. one day before being challenged by infected Ixodes nymphs.  Three weeks after the challenge, mouse tissue samples of ear, ankle joint, heart and bladder were collected, cultured and examined for growth of Borreliafor 4 weeks by dark field microscopy and by qPCR using primers specific for OspA.  Both 221-7 and 319-44 completely protected mice from infection at doses >5 mg/kg and partially protected from infection at 1 mg/kg.  Protection was dependent upon serum antibody levels and mice with >2-3ug/ml at three weeks post challenge were protected.  Synergy between antibodies was not observed when both antibodies were administered together at suboptimal doses despite binding to distinct epitopes. 

    Conclusion: Our study demonstrates that HuMabs 319-44 and 221-7 can prevent the transmission of Borrelia from ticks to mice and supports exploring PrEP using anti-OspA antibodies as passive immunoprophylaxis to prevent Lyme disease.

    Yang Wang, MD PhD1, Aurélie Kern, PhD2, Andrew Sadowski, BA1, Naomi K. Boatright, BA1, Linden Hu, MD2, William Thomas Jr., PhD1 and Mark S. Klempner, MD1, (1)MassBiologics of the University of Massachusetts Medical School, Boston, MA, (2)Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA

    Disclosures:

    Y. Wang, None

    A. Kern, None

    A. Sadowski, None

    N. K. Boatright, None

    L. Hu, None

    W. Thomas Jr., None

    M. S. Klempner, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.