Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes
Bacterial Infections and Mycoses | Immunoprophylaxis and Therapy | Public Health | Translational Medical Research
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: 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: 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: 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.
UMCCTS funding, Lyme disease, OspA, human monoclonal antibody, preexposure prophylaxis
DOI of Published Version
J Infect Dis. 2016 Jul 15;214(2):205-11. doi: 10.1093/infdis/jiw151. Epub 2016 Apr 18. Link to article on publisher's site
The Journal of infectious diseases
Wang, Yan; Kern, Aurelie; Boatright, Naomi; Schiller, Zachary; Sadowski, Andrew; Monir, Ejemel; Souders, Colby; Reimann, Keith A.; Hu, Linden; Thomas, William D. Jr.; and Klempner, Mark S., "Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes" (2016). UMass Center for Clinical and Translational Science Supported Publications. 117.