Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20
- Department of Biochemistry and Molecular Biology, School of Medicine, Mail code L224, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098 (United States)
- Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4380 (United States)
- Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295 (United States)
The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5 A resolution is determined for a complex of AAV-2 with the Fab' fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells.
- OSTI ID:
- 22149291
- Journal Information:
- Virology, Journal Name: Virology Journal Issue: 1-2 Vol. 431; ISSN VIRLAX; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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