Structural and Molecular Analysis of a Protective Epitope of Lyme Disease Antigen OspA and Antibody Interactions
Authors
Shandilya, ShivenderYilmaz, Nese Kurt
Monir, Ejemel
Sadowski, Andrew
Thomas, William D.
Klempner, Mark S.
Schiffer, Celia A.
Wang, Yan
Document Type
Poster AbstractPublication Date
2016-05-20Keywords
lyme diseaseborrelia burgdorferi
OspA
outer surface protein
Bacterial Infections and Mycoses
Biochemistry
Biological Factors
Immunity
Immunology of Infectious Disease
Molecular Biology
Structural Biology
Metadata
Show full item recordAbstract
The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease. Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 based on computational predictions on the crystal structure of the complex, and experimentally tested for in-vitro binding and borreliacidal activity. We find that Y32 and H49 on the LA-2 light chain, N52 on the LA-2 heavy chain and residues A208, N228 and N251 on OspA were the key constituents of OspA/LA-2 interface. These results reveal specific residues that may be exploited to modulate recognition of the protective epitope of OspA and have implications for design of vaccines against Lyme disease.DOI
10.13028/vz14-5956Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28115Rights
Copyright the Author(s)Distribution License
http://creativecommons.org/licenses/by-nc-sa/3.0/ae974a485f413a2113503eed53cd6c53
10.13028/vz14-5956