Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes
Authors
Wang, YanKern, Aurelie
Boatright, Naomi
Schiller, Zachary
Sadowski, Andrew
Monir, Ejemel
Souders, Colby
Reimann, Keith A.
Hu, Linden
Thomas, William D. Jr.
Klempner, Mark S.
UMass Chan Affiliations
MassBiologicsDocument Type
Journal ArticlePublication Date
2016-07-15Keywords
UMCCTS fundingLyme disease
OspA
human monoclonal antibody
preexposure prophylaxis
Bacterial Infections and Mycoses
Immunoprophylaxis and Therapy
Public Health
Translational Medical Research
Metadata
Show full item recordAbstract
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.Source
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 siteDOI
10.1093/infdis/jiw151Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50288PubMed ID
27338767Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1093/infdis/jiw151