Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model
Kei Amemiya,
Jennifer L. Dankmeyer,
Sarah L. Keasey,
Sylvia R. Trevino,
Michael M. Wormald,
Stephanie A. Halasohoris,
Wilson J. Ribot,
David P. Fetterer,
Christopher K. Cote,
Patricia L. Worsham,
Jeffrey J. Adamovicz,
Robert G. Ulrich
Affiliations
Kei Amemiya
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Jennifer L. Dankmeyer
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Sarah L. Keasey
Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Sylvia R. Trevino
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Michael M. Wormald
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Stephanie A. Halasohoris
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Wilson J. Ribot
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
David P. Fetterer
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Christopher K. Cote
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Patricia L. Worsham
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Jeffrey J. Adamovicz
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
Robert G. Ulrich
Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
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.
