title: Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes.
abstract: Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States.
  
  
  
  Mice transgenic for human immunoglobulin genes were immunized with OspA from B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays.
  
  
  
  Nearly 100 unique OspA-specific HuMabs were generated, and 4 HuMabs (221-7, 857-2, 319-44, and 212-55) were selected as lead candidates on the basis of borreliacidal activity. HuMabs 319-44, 857-2, and 212-55 were borreliacidal against 1 or 2 Borrelia genospecies, whereas 221-7 was borreliacidal (half maximal inhibitory concentration, < 1 nM) against B. burgdorferi, Borrelia afzelii, and Borrelia garinii, the 3 main genospecies endemic in the United States, Europe, and Asia. All 4 HuMabs completely protected mice from infection at 10 mg/kg in a murine model of tick-mediated transmission of B. burgdorferi
  
  
  
  Our study indicates that OspA-specific HuMabs can prevent the transmission of Borrelia and that administration of these antibodies could be employed as preexposure prophylaxis for Lyme disease.
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kern
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Naomi K
authors.initials: NK
authors.lastname: Boatright
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Schiller
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sadowski
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Monir
authors.initials: M
authors.lastname: Ejemel
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Colby A
authors.initials: CA
authors.lastname: Souders
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.affiliation: Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Linden
authors.initials: L
authors.lastname: Hu
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: William D
authors.initials: WD
authors.lastname: Thomas
authors.affiliation: MassBiologics, University of Massachusetts Medical School.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Klempner
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage* / Q000302:isolation & purification; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000302:isolation & purification; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors*; D001428:Bacterial Vaccines / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D007116:Immunization, Passive / Q000379:methods; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000302:isolation & purification; D008074:Lipoproteins / Q000037:antagonists & inhibitors*; D008193:Lyme Disease / Q000517:prevention & control* / Q000635:transmission; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D064927:Tick Bites / Q000150:complications; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007155:Immunologic Factors; D008074:Lipoproteins; C072045:OspA protein
keywords: Lyme disease; OspA; human monoclonal antibody; preexposure prophylaxis