Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against Yersinia pestis Infection in a Bubonic Plague Model
Abstract
Plague is a zoonotic disease that is caused by Yersinia pestis. Monoclonal antibodies (mAbs) that bind to the V-antigen, a virulence factor that is produced by Y. pestis, can passively protect mice from plague. An analysis of protective mAbs that bind to V-antigen was made to assess binding sites, avidities, and affinities. Anti-V mAbs were screened for their efficacy in a murine model of plague. Antigen-binding sites of protective V mAbs were determined with a linear peptide library, V-antigen fragment, competitive binding, and surface plasmon resonance. The avidities to the V-antigen was determined by ELISA, and affinities of the mAbs to the V-antigen were determined by surface plasmon resonance. The most protective mAb 7.3 bound to a unique conformational site on the V-antigen, while a less protective mAb bound to a different conformational site located on the same V-antigen fragment as mAb 7.3. The avidity of mAb 7.3 for the V-antigen was neither the strongest overall nor did it have the highest affinity for the V-antigen. The binding site of the most protective mAb was critical in its ability to protect against a lethal plague challenge.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 03, 2020
- Source ID
- 10.3390/antib9030037
Entities
People
- Christopher K Cote
- David P. Fetterer
- Jeffrey J. Adamovicz
- Jennifer L. Dankmeyer
- Kei Amemiya
- Michael M. Wormald
- Patricia L. Worsham
- Robert G Ulrich
- Sarah L. Keasey
- Stephanie A. Halasohoris
- Sylvia R. Treviño
- Wilson J. Ribot
Organizations
- Defense Threat Reduction Agency