Despite causing many of the most devastating epidemics in history, Yersinia pestishas never been eradicated. This gives Y. pestisdangerous potential as a biological weapon, necessitating research into effective treatments and vaccines. Monoclonal antibodies (mAbs) have been proposed as effective protective agents against the plague, but before this 2017 paper by Liu et al. only one mAb had been confirmed to prevent spread of Y. pestis.
In this paper, the authors present F2H5, a mAb that protects against Y. pestisinfection in a mouse model. Previous studies of mAbs in Y. Pestis prevention focused on antibodies that bind to the bacterial F1 protein, so the authors immunized mice with recombinant F1 (rF1) and used ELISA to obtain three monoclonal antibody lines with therapeutic potential. They then tested the effectiveness of each mAb by first pre-treating mice with an antibody, and subsequently infecting them with Y. pestis; they found that F2H5 provided complete protection against Y. pestisinfection. Once they observed the antibacterial effects of F2H5, they used ELISA and Western Blot to confirm that the mAb bound selectively to rF1.
Once they had identified and verified F2H5, the authors used computational methods to investigate the epitope to which the mAb binds. Using a novel method called Residue Contact Frequency (RCF), the researchers were able to predict the F1 epitopes most likely to be recognized by F2H5. They then verified the top RCF result using Western Blot, mutating amino acids in the region until they identified a three-residue sequence essential for F2H5 to bind to F1. They then used computational technology to characterize the F1/F2H5 complex and the effect of F1 mutations on its structure.
This paper provides a novel antibody which could be used to protect against a dangerous bioweapon. The authors were able to confirm its efficacy in a mouse model and humanize it for future therapeutic use. In addition, by identifying the epitope and predicting the dynamics of the antibody-antigen complex, the authors verified their assessment of therapeutic potential.
By: Zach Altshuler
Liu, W. et al.Identification and characterization of a neutralizing monoclonal antibody that provides complete protection against Yersinia pestis. PLOS ONE, e0177012 (2017).