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.
A. Sadowski, None
N. K. Boatright, None
L. Hu, None
W. Thomas Jr., None
M. S. Klempner, None