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.
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.
['Amemiya|Kei|K|', 'Dankmeyer|Jennifer L|JL|', 'Keasey|Sarah L|SL|', 'Trevino|Sylvia R|SR|', 'Wormald|Michael M|MM|', 'Halasohoris|Stephanie A|SA|', 'Ribot|Wilson J|WJ|', 'Fetterer|David P|DP|', 'Cote|Christopher K|CK|', 'Worsham|Patricia L|PL|', 'Adamovicz|Jeffrey J|JJ|', 'Ulrich|Robert G|RG|']
binding sites monoclonal antibodies avidities affinities passive protection Yersinia pestis plague