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7052611 
Journal Article 
Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes 
Wang, Y; Thomas, WD, Jr; Klempner, MS; Kern, A; Boatright, NK; Schiller, ZA; Sadowski, A; Ejemel, M; Souders, CA; Reimann, KA; Hu, L; , 
2016 
Yes 
Journal of Infectious Diseases
ISSN: 0022-1899
EISSN: 1537-6613 
OXFORD UNIV PRESS INC 
CARY 
214 
2 
205-211 
English 
27338767 
WOS:000379822900007 
Background. 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.Methods.aEuro integral 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.Results.aEuro integral 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.Conclusions.aEuro integral 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. 
Lyme disease; OspA; human monoclonal antibody; preexposure prophylaxis